Metastasis - Knowledge

455:

new hypotheses were suggested as well, i.e., under the effect of particular biochemical and/or physical stressors, cancer cells can undergo nuclear expulsion with subsequent macrophage engulfment and fusion, with the formation of cancer fusion cells (CFCs). Understanding the enigma of cancer cell spread to distant sites, which accounts for over 90% of cancer-related deaths, necessitates comprehensive investigation. Key outstanding questions revolve around the survival and migration of cancer cells, such as the nucleus, as they face challenges in passage through capillary valves and hydrodynamic shear forces in the circulation system, making CTCs an unlikely source of metastasis. Moreover, understanding how cancer cells adapt to the metastatic niche and remain dormant (tumor dormancy) for extended periods presents difficult questions that require further investigation.

306: 527:(ID1). This novel finding meant that investigators gained the ability to track endothelial progenitor cells from the bone marrow to the blood to the tumor-stroma and even incorporated in tumor vasculature. Endothelial progenitor cells incorporated in tumor vasculature suggests that this cell type in blood-vessel development is important in a tumor setting and metastasis. Furthermore, ablation of the endothelial progenitor cells in the bone marrow can lead to a significant decrease in tumor growth and vasculature development. Therefore, endothelial progenitor cells are important in tumor biology and present novel therapeutic targets. The immune system is typically deregulated in cancer and affects many stages of tumor progression, including metastasis. 945: 1001: 813: 925: 680: 619: 1040: 971: 472:(ECM), which separates the tumor from adjoining tissues. By degrading these proteins, cancer cells are able to breach the ECM and escape. The location of the metastases is not always random, with different types of cancer tending to spread to particular organs and tissues at a rate that is higher than expected by statistical chance alone. Breast cancer, for example, tends to metastasize to the bones and lungs. This specificity seems to be mediated by soluble signal molecules such as 72: 1052: 986: 1226: 1028: 1103:, or a combination of these interventions ("multimodal therapy"). The choice of treatment depends on many factors, including the type of primary cancer, the size and location of the metastases, the patient's age and general health, and the types of treatments used previously. In patients diagnosed with CUP it is often still possible to treat the disease even when the primary tumor cannot be located. 1240: 454:

Currently, three main theories have been proposed to explain the metastatic pathway of cancer: the epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) hypothesis (1), the cancer stem cell hypothesis (2), and the macrophage–cancer cell fusion hybrid hypothesis (3). Some

1067:

Treatment and survival is determined, to a great extent, by whether or not a cancer remains localized or spreads to other locations in the body. If the cancer metastasizes to other tissues or organs it usually dramatically increases a patient's likelihood of death. Some cancers—such as some forms of

533:

regulation also plays an important role in the metastatic outgrowth of disseminated tumor cells. Metastases display alterations in histone modifications, such as H3K4-methylation and H3K9-methylation, when compared to matching primary tumors. These epigenetic modifications in metastases may allow

754:

challenged the "seed and soil" theory and proposed that metastasis occurs purely by anatomic and mechanical routes. This hypothesis has been recently utilized to suggest several hypotheses about the life cycle of circulating tumor cells (CTCs) and to postulate that the patterns of spread could be

889:

down-regulation was also associated with the signature. Additionally, the metastatic-associated expression of these genes was also observed in some primary tumors, indicating that cells with the potential to metastasize could be identified concurrently with diagnosis of the primary tumor. Recent

582:

near the primary tumor and ultimately, to other parts of the body. This is called nodal involvement, positive nodes, or regional disease. "Positive nodes" is a term that would be used by medical specialists to describe regional lymph nodes that tested positive for malignancy. It is common medical

537:

A recent study shows that PKC-iota promotes melanoma cell invasion by activating Vimentin during EMT. PKC-iota inhibition or knockdown resulted in an increase in E-cadherin and RhoA levels while decreasing total Vimentin, phosphorylated Vimentin (S39) and Par6 in metastatic melanoma cells. These

828:

cells look the same whether they are found in the breast or have spread to another part of the body. So, if a tissue sample taken from a tumor in the lung contains cells that look like breast cells, the doctor determines that the lung tumor is a secondary tumor. Still, the determination of the

502:

All steps of the metastatic cascade involve a number of physical processes. Cell migration requires the generation of forces, and when cancer cells transmigrate through the vasculature, this requires physical gaps in the blood vessels to form. Besides forces, the regulation of various types of

917:

The identification of this metastasis-associated signature provides promise for identifying cells with metastatic potential within the primary tumor and hope for improving the prognosis of these metastatic-associated cancers. Additionally, identifying the genes whose expression is changed in

759:

at distant sites, where incoming metastatic cells may engraft and colonise. Specifically, exosome vesicles secreted by tumours have been shown to home to pre-metastatic sites, where they activate pro-metastatic processes such as angiogenesis and modify the immune contexture, so as to foster a

463:

Metastasis involves a complex series of steps in which cancer cells leave the original tumor site and migrate to other parts of the body via the bloodstream, via the lymphatic system, or by direct extension. To do so, malignant cells break away from the primary tumor and attach to and degrade

844:

It was previously thought that most cancer cells have a low metastatic potential and that there are rare cells that develop the ability to metastasize through the development of somatic mutations. According to this theory, diagnosis of metastatic cancers is only possible after the event of

897:

Expression of this metastatic signature has been correlated with a poor prognosis and has been shown to be consistent in several types of cancer. Prognosis was shown to be worse for individuals whose primary tumors expressed the metastatic signature. Additionally, the expression of these

820:

The cells in a metastatic tumor resemble those in the primary tumor. Once the cancerous tissue is examined under a microscope to determine the cell type, a doctor can usually tell whether that type of cell is normally found in the part of the body from which the tissue sample was taken.

1120:, care aimed at improving the quality of life of people with major illness, has been recommended as part of management programs for metastasis. Results from a systematic review of the literature on radiation therapy for brain metastases found that there is little evidence to inform 856:

mutation theory of metastasis development has not been substantiated in human cancers. Rather, it seems that the genetic state of the primary tumor reflects the ability of that cancer to metastasize. Research comparing gene expression between primary and metastatic

1140:

saying that some metastases are the result of inflammatory processes by abnormal immune cells. The existence of metastatic cancers in the absence of primary tumors also suggests that metastasis is not always caused by malignant cells that leave primary tumors.

499:. Cancer cells often opportunistically switch between different kinds of motion. Some cancer researchers hope to find treatments that can stop or at least slow down the spread of cancer by somehow blocking some necessary step in one or more kinds of motion. 722:

According to the "seed and soil" theory, it is difficult for cancer cells to survive outside their region of origin, so in order to metastasize they must find a location with similar characteristics. For example, breast tumor cells, which gather calcium

894:(CIN) as a driver of metastasis. In aggressive cancer cells, loose DNA fragments from unstable chromosomes spill in the cytosol leading to the chronic activation of innate immune pathways, which are hijacked by cancer cells to spread to distant organs. 840:

Metastatic cancers may be found at the same time as the primary tumor, or months or years later. When a second tumor is found in a patient that has been treated for cancer in the past, it is more often a metastasis than another primary tumor.

667:. The process is similar to that of transcoelomic spread. However, often it remains unclear whether simultaneously diagnosed tumors of a canalicular system are one metastatic process or in fact independent tumors caused by the same agent ( 1156:

of melanoma cells is important for its metastasis and growth: non-pigmented tumors were bigger than pigmented and it was much easier for them to spread. They showed that there are both pigmented and non-pigmented cells in melanoma

241:

spread. After the tumor cells come to rest at another site, they re-penetrate the vessel or walls and continue to multiply, eventually forming another clinically detectable tumor. This new tumor is known as a metastatic (or

924: 506:

The metastatic steps are critically regulated by various cell types, including the blood vessel cells (endothelial cells), immune cells or stromal cells. The growth of a new network of blood vessels, called tumor

768:

It is theorized that metastasis always coincides with a primary cancer, and, as such, is a tumor that started from a cancer cell or cells in another part of the body. However, over 10% of patients presenting to

541:

Recently, a series of high-profile experiments suggests that the co-option of intercellular cross-talk mediated by exosome vesicles is a critical factor involved in all steps of the invasion-metastasis cascade.

804:. It is therefore thought that some primary tumors can regress completely, but leave their metastases behind. In other cases, the tumor might just be too small and/or in an unusual location to be diagnosed. 944: 436:

Metastatic tumors are very common in the late stages of cancer. The spread of metastasis may occur via the blood or the lymphatics or through both routes. The most common sites of metastases are the

1459: 523:

have been shown to have a strong influence on metastasis and angiogenesis. Endothelial progenitor cells are important in tumor growth, angiogenesis and metastasis, and can be marked using the

1000: 781:(UPT). It is estimated that 3% of all cancers are of unknown primary origin. Studies have shown that, if simple questioning does not reveal the cancer's source (coughing up blood—"probably 755:

better understood through a 'filter and flow' perspective. However, contemporary evidences indicate that the primary tumour may dictate organotropic metastases by inducing the formation of

861:

identified a subset of genes whose expression could distinguish primary tumors from metastatic tumors, dubbed a "metastatic signature." Up-regulated genes in the signature include:

1184:

In March 2014 researchers discovered the oldest complete example of a human with metastatic cancer. The tumors had developed in a 3,000-year-old skeleton found in 2013 in a tomb in

2340:"Two novel atypical PKC inhibitors; ACPD and DNDA effectively mitigate cell proliferation and epithelial to mesenchymal transition of metastatic melanoma while inducing apoptosis" 796:

has permitted pathologists to give an identity to many of these metastases. However, imaging of the indicated area only occasionally reveals a primary. In rare cases (e.g., of

2926:

Irwin KE, Greer JA, Khatib J, Temel JS, Pirl WF (February 2013). "Early palliative care and metastatic non-small cell lung cancer: potential mechanisms of prolonged survival".

2191:"Using the transcription factor inhibitor of DNA binding 1 to selectively target endothelial progenitor cells offers novel strategies to inhibit tumor angiogenesis and growth" 639:

and follicular carcinomas of the thyroid. Because of their thinner walls, veins are more frequently invaded than are arteries, and metastasis tends to follow the pattern of

595:

to metastasize via this route. Localized spread to regional lymph nodes near the primary tumor is not normally counted as a metastasis, although this is a sign of a worse

2089:

Gao D, Nolan DJ, Mellick AS, Bambino K, McDonnell K, Mittal V (January 2008). "Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis".

168:

agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a

2427: 297:, metastasis places a cancer in Stage IV. The possibilities of curative treatment are greatly reduced, or often entirely removed when a cancer has metastasized. 773:

will have metastases without a primary tumor found. In these cases, doctors refer to the primary tumor as "unknown" or "occult," and the patient is said to have

2392:

Syn N, Wang L, Sethi G, Thiery JP, Goh BC (July 2016). "Exosome-Mediated Metastasis: From Epithelial-Mesenchymal Transition to Escape from Immunosurveillance".

583:

practice to test by biopsy at least one lymph node near a tumor site when carrying out surgery to examine or remove a tumor. This lymph node is then called a

3301: 1469: 3006:"A new hypothesis: some metastases are the result of inflammatory processes by adapted cells, especially adapted immune cells at sites of inflammation" 2816:, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, et al. (January 2002). "Gene expression profiling predicts clinical outcome of breast cancer". 277:

metastasizes to the lungs, the secondary tumor is made up of abnormal breast cells, not of abnormal lung cells. The tumor in the lung is then called

3330: 233:, after which they are able to circulate through the bloodstream to other sites and tissues in the body. This process is known (respectively) as 849:) would only investigate a subpopulation of the cancer cells and would very likely not sample from the subpopulation with metastatic potential. 663:

may metastasize along anatomical canalicular spaces. These spaces include for example the bile ducts, the urinary system, the airways and the

1188:

dating back to 1200 BC. The skeleton was analyzed using radiography and a scanning electron microscope. These findings were published in the

2969:

Garsa A, Jang JK, Baxi S, Chen C, Akinniranye O, Hall O, et al. (2021). "Radiation Therapy for Brain Metastases: A Systematic Review".

538:

results suggested that PKC-ι is involved in signaling pathways which upregulate EMT in melanoma thereby directly stimulates metastasis.

3164:

Zarshenas MM, Mohammadi-Bardbori A (February 2017). "A medieval description of metastatic breast cancer; from Avicenna's view point".

1289: 695:

There is a propensity for certain tumors to seed in particular organs. This was first discussed as the "seed and soil" theory by

2439:

Ribatti D, Mangialardi G, Vacca A (December 2006). "Stephen Paget and the 'seed and soil' theory of metastatic dissemination".

305: 187:

Cancer occurs after cells are genetically altered to proliferate rapidly and indefinitely. This uncontrolled proliferation by

2534: 1559: 643:. That is, hematogenous spread often follows distinct patterns depending on the location of the primary tumor. For example, 631:

This is typical route of metastasis for sarcomas, but it is also the favored route for certain types of carcinoma, such as

1039: 2770:

Ramaswamy S, Ross KN, Lander ES, Golub TR (January 2003). "A molecular signature of metastasis in primary solid tumors".

420:

Some patients, however, do not show any symptoms. When the organ gets a metastatic disease it begins to shrink until its

3057:"The migration ability of stem cells can explain the existence of cancer of unknown primary site. Rethinking metastasis" 1173:

The first physician to report the possibility of local metastasis from a primary cancerous source to nearby tissues was

1981:"Balance of mechanical forces drives endothelial gap formation and may facilitate cancer and immune-cell extravasation" 1121: 970: 699:

in 1889. The propensity for a metastatic cell to spread to a particular organ is termed 'organotropism'. For example,

834: 1051: 829:

primary tumor can often be very difficult, and the pathologist may have to use several adjuvant techniques, such as

622:

Lymph node with almost complete replacement by metastatic melanoma. The brown pigment is focal deposition of melanin

3452: 774: 1748:

Zlotnik A, Burkhardt AM, Homey B (August 2011). "Homeostatic chemokine receptors and organ-specific metastasis".

477: 2240:"Biomarkers of residual disease, disseminated tumor cells, and metastases in the MMTV-PyMT breast cancer model" 214:

phenotype. This malignancy allows for invasion into the circulation, followed by invasion to a second site for

2142:"Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization" 3767: 1345: 480:. The body resists metastasis by a variety of mechanisms through the actions of a class of proteins known as 1300: 1294: 3249: 954: 520: 17: 3798: 3340: 1624: 727:

from breast milk, metastasize to bone tissue, where they can gather calcium ions from bone. Malignant

294: 3839: 3592: 3335: 1269: 1190: 1125: 1027: 985: 751: 3349: 3302:"Possible Oldest Cancer Found In 3,000-Year-Old Skeleton Could Reveal 'Evolution' Of Modern Disease" 2720: 1936:

Friedl P, Wolf K (May 2003). "Tumour-cell invasion and migration: diversity and escape mechanisms".

1263: 837:), and others. Despite the use of techniques, in some cases the primary tumor remains unidentified. 3627: 3585: 3378: 615:, and therefore these metastatic cells can also eventually spread through the haematogenous route. 368: 2613:

Ettinger DS, Agulnik M, Cates JM, Cristea M, Denlinger CS, Eaton KD, et al. (December 2011).

3720: 3684: 3622: 1136:

Although metastasis is widely accepted to be the result of the tumor cells migration, there is a

512: 247: 1979:

Escribano J, Chen MB, Moeendarbary E, Cao X, Shenoy V, Garcia-Aznar JM, et al. (May 2019).

3725: 3679: 2813: 2715: 1152:

about 4.93, when in non-pigmented ones it was only 0.98. In another experiment they found that

891: 778: 516: 222: 3418: 789:"), complex imaging will not either. In some of these cases a primary tumor may appear later. 3777: 3758: 1274: 1178: 812: 481: 341: 33: 3730: 3575: 3565: 3445: 3120: 2882: 2707: 2251: 2140:

Nolan DJ, Ciarrocchi A, Mellick AS, Jaggi JS, Bambino K, Gupta S, et al. (June 2007).

2098: 2002: 1279: 1153: 830: 793: 756: 632: 612: 604: 558:

The spread of a malignancy into body cavities can occur via penetrating the surface of the

469: 255: 195: 3430: 2189:

Mellick AS, Plummer PN, Nolan DJ, Gao D, Bambino K, Hahn M, et al. (September 2010).

1576: 184:, which is the direct extension and penetration by cancer cells into neighboring tissues. 8: 3617: 3549: 2869:

Bakhoum SF, Ngo B, Laughney AM, Cavallo JA, Murphy CJ, Ly P, et al. (January 2018).

1106:

Current treatments are rarely able to cure metastatic cancer though some tumors, such as

668: 584: 3275: 3124: 2886: 2711: 2566:"Unifying metastasis--integrating intravasation, circulation and end-organ colonization" 2544: 2255: 2102: 2006: 1320: 3710: 3225: 3200: 3141: 3109:"Melanin presence inhibits melanoma cell spread in mice in a unique mechanical fashion" 3108: 3081: 3056: 3032: 3005: 2951: 2903: 2870: 2851: 2795: 2741: 2590: 2565: 2549: 2507: 2464: 2364: 2339: 2274: 2239: 2215: 2190: 2166: 2141: 2122: 2025: 1992: 1980: 1961: 1913: 1886: 1817: 1792: 1773: 1730: 1678: 1653: 1520: 1495: 1436: 1411: 1388: 1149: 1092: 683:

Main sites of metastases for some common cancer types. Primary cancers are denoted by "

664: 290: 679: 618: 3844: 3813: 3803: 3715: 3529: 3389: 3230: 3181: 3146: 3086: 3037: 2986: 2943: 2908: 2843: 2787: 2733: 2680: 2636: 2595: 2530: 2499: 2482:

Hart IR (1982). "'Seed and soil' revisited: mechanisms of site-specific metastasis".

2456: 2409: 2369: 2320: 2279: 2220: 2171: 2114: 2071: 2030: 1953: 1918: 1867: 1822: 1765: 1722: 1683: 1555: 1525: 1441: 1392: 1380: 1266:(Sections on cavernous malformation, germinoma, renal cell carcinoma and lung cancer) 1107: 1088: 853: 644: 559: 496: 407: 314: 148: 37: 2799: 2511: 2468: 2126: 1777: 1734: 898:

metastatic-associated genes was shown to apply to other cancer types in addition to

350: 3702: 3580: 3220: 3212: 3173: 3136: 3128: 3076: 3068: 3027: 3017: 2978: 2955: 2935: 2898: 2890: 2855: 2833: 2825: 2779: 2745: 2725: 2670: 2626: 2585: 2577: 2491: 2448: 2401: 2359: 2351: 2310: 2269: 2259: 2210: 2202: 2161: 2153: 2106: 2061: 2020: 2010: 1965: 1945: 1908: 1898: 1857: 1812: 1804: 1757: 1714: 1673: 1665: 1515: 1507: 1464: 1431: 1423: 1372: 1258: 1203: 716: 399: 226: 93: 3022: 2675: 2658: 2206: 1702: 1654:"The natural adaptive evolution of cancer: The metastatic ability of cancer cells" 1407: 3818: 3793: 3438: 3383: 3177: 2264: 2015: 1491: 1284: 1253: 1245: 1162: 1117: 1096: 911: 907: 858: 700: 389: 345: 181: 2426:

List of included entries and references is found on main image page in Commons:

2066: 2049: 3740: 3698: 3394: 3132: 2982: 2405: 1231: 1111: 1014: 899: 786: 708: 567: 563: 286: 2452: 2238:

Franci C, Zhou J, Jiang Z, Modrusan Z, Good Z, Jackson E, et al. (2013).

1862: 1845: 1808: 1511: 534:

the proliferation and survival of disseminated tumor cells in distant organs.

3833: 3544: 3072: 2939: 2050:"Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma" 1669: 903: 825: 770: 696: 600: 274: 270: 215: 192: 3107:

Sarna M, Krzykawska-Serda M, Jakubowska M, Zadlo A, Urbanska K (June 2019).

2871:"Chromosomal instability drives metastasis through a cytosolic DNA response" 2698:

Poste G, Fidler IJ (January 1980). "The pathogenesis of cancer metastasis".

2631: 2614: 2110: 1846:"Metastasis-suppressor genes: a review and perspective on an emerging field" 1376: 45: 3485: 3234: 3216: 3185: 3150: 3090: 3041: 2990: 2947: 2912: 2847: 2791: 2684: 2640: 2599: 2460: 2413: 2373: 2338:

Ratnayake WS, Apostolatos AH, Ostrov DA, Acevedo-Duncan M (November 2017).

2324: 2283: 2224: 2175: 2118: 2034: 1957: 1922: 1903: 1871: 1826: 1769: 1726: 1687: 1529: 1445: 1384: 1084: 1080: 1018: 962: 886: 704: 640: 608: 508: 372: 251: 230: 2737: 2503: 2355: 2075: 1427: 914:

all had similar expression patterns of these metastasis-associated genes.

71: 3808: 3748: 3607: 3570: 3493: 3413: 1841: 1073: 938:

metastasis (the whitish tumor between the head and the shaft of the bone)

782: 648: 530: 421: 2894: 2337: 2315: 2299:"How epigenetics can explain human metastasis: a new role for microRNAs" 2298: 3753: 3602: 3503: 2495: 2157: 1137: 1128:

outcomes on quality of life, functional status, and cognitive effects.

958: 950: 736: 579: 492: 473: 358: 211: 199: 3370: 2838: 1652:

Olteanu GE, Mihai IM, Bojin F, Gavriliuc O, Paunescu V (August 2020).

1496:"Circulating tumor cells: a window into cancer biology and metastasis" 587:. Lymphatic spread is the most common route of initial metastasis for 3772: 3658: 3643: 3524: 3508: 2729: 740: 660: 596: 588: 403: 207: 203: 3106: 2829: 2581: 1949: 1839: 1793:"TGF-β signaling in breast cancer cell invasion and bone metastasis" 1761: 1718: 3762: 3653: 3612: 3597: 3470: 3462: 2783: 1997: 1225: 1177:. He described a case of breast cancer and metastatic condition in 1174: 1158: 1145: 1069: 797: 728: 488: 393: 384: 165: 153: 503:

cell-cell and cell-matrix adhesions is crucial during metastasis.

3663: 3648: 2812: 2545:"Basics: A mutinous group of cells on a greedy, destructive task" 1100: 991: 976: 931: 874: 801: 592: 578:

Lymphatic spread allows the transport of tumor cells to regional

465: 362: 188: 1144:

The research done by Sarna's team proved that heavily pigmented

3534: 3466: 3250:"Archaeologists discover earliest example of human with cancer" 1010: 935: 890:

work identified a form of genetic instability in cancer called

882: 866: 846: 744: 732: 636: 380: 169: 3276:"Ancient skeleton is the earliest case of cancer yet detected" 3201:"Avicenna's Concepts on Cancer Metastasis from the 11 Century" 1181:. His hypothesis was based on clinical course of the patient. 129: 1363:

Klein CA (September 2008). "Cancer. The metastasis cascade".

1185: 1007: 878: 862: 712: 445: 441: 425: 376: 354: 329: 325: 321: 310: 269:

tumor, and its cells are similar to those in the original or

254:. Most cancers can metastasize, although in varying degrees. 2428:

Commons:File:Metastasis sites for common cancers.svg#Summary

1978: 1079:

Once a cancer has metastasized it may still be treated with

845:

metastasis. Traditional means of diagnosing cancer (e.g. a

336:

are the most common metastasis locations from solid tumors.

3498: 3460: 3163: 2612: 2139: 1550:

Kumar V, Abbas AK, Fausto N, Robbins SL, Cotran RS (2005).

918:

metastasis offers potential targets to inhibit metastasis.

870: 449: 437: 414: 333: 313:

showing multiple paler metastatic nodules originating from

121: 99: 2048:

Weidner N, Semple JP, Welch WR, Folkman J (January 1991).

1651: 570:

can spread transperitoneally to the surface of the liver.

487:

Human cells exhibit different kinds of motion: collective

198:. The cells which constitute the tumor eventually undergo 2868: 2047: 1705:(May 2007). "Genetic determinants of cancer metastasis". 760:

favourable microenvironment for secondary tumour growth.

724: 524: 110: 2769: 703:

usually metastasizes to the bones. In a similar manner,

261:

When tumor cells metastasize, the new tumor is called a

2438: 2237: 1549: 599:. The lymphatic system does eventually drain from the 2188: 2088: 2925: 1887:"Rac and Rho GTPases in cancer cell motility control" 1747: 132: 126: 113: 3360: 3339:. U.S. National Institutes of Health. Archived from 2619:

Journal of the National Comprehensive Cancer Network

1221: 566:, pericardial, or subarachnoid spaces. For example, 320:

Initially, nearby lymph nodes are struck early. The

118: 107: 1468:. Australian Government. 2014-12-16. Archived from 104: 96: 2656: 2615:"NCCN Clinical Practice Guidelines Occult primary" 2391: 687:" and their main metastasis sites are denoted by " 2968: 2652: 2650: 2563: 1554:(7th ed.). Philadelphia: Elsevier Saunders. 3831: 2296: 1790: 1352:. American Cancer Society, Inc. 2 February 2016. 763: 550:Metastasis occurs by the following four routes: 172:tumor. The newly pathological sites, then, are 1647: 1645: 1489: 3241: 2647: 1797:Journal of Mammary Gland Biology and Neoplasia 1700: 1552:Robbins and Cotran pathologic basis of disease 1405: 225:acquire the ability to penetrate the walls of 3446: 3102: 3100: 1884: 1500:Current Opinion in Genetics & Development 3267: 3198: 3054: 2765: 2763: 2761: 2759: 2757: 2755: 2331: 2133: 2082: 1784: 1741: 1642: 707:has a tendency to metastasize to the liver. 79:Illustration showing hematogenous metastasis 3293: 2697: 2387: 2385: 2383: 1694: 3453: 3439: 3097: 3003: 2919: 2564:Scott J, Kuhn P, Anderson AR (July 2012). 2557: 1935: 1625:"Metastatic Cancer: Questions and Answers" 406:symptoms such as headaches, seizures, and 70: 3224: 3140: 3080: 3031: 3021: 2902: 2837: 2752: 2719: 2674: 2630: 2589: 2475: 2363: 2314: 2273: 2263: 2214: 2165: 2065: 2024: 2014: 1996: 1912: 1902: 1861: 1816: 1677: 1658:Bosnian Journal of Basic Medical Sciences 1545: 1543: 1541: 1539: 1519: 1435: 1057:Metastases from the lungs to the pancreas 816:Pulmonary metastases shown on Chest X-Ray 731:spreads to the brain, presumably because 674: 2524: 2380: 2297:Lujambio A, Esteller M (February 2009). 1850:Journal of the National Cancer Institute 1338: 1290:Mouse models of breast cancer metastasis 1206:word meaning "displacement", from μετά, 811: 678: 617: 519:would prevent the growth of metastases. 304: 3247: 1844:, Rinker-Schaeffer CW (November 2000). 607:into the systemic venous system at the 14: 3832: 2542: 1885:Parri M, Chiarugi P (September 2010). 1619: 1617: 1536: 1045:Metastases from the lungs to the brain 800:), no primary tumor is found, even on 626: 180:). It is generally distinguished from 3434: 3273: 1615: 1613: 1611: 1609: 1607: 1605: 1603: 1601: 1599: 1597: 1362: 654: 515:It has therefore been suggested that 417:, it is often not the first symptom. 300: 40:. For the Spanish-language remake of 3350:"How does cancer spread – the route" 3299: 2481: 1791:Drabsch Y, ten Dijke P (June 2011). 1631:. U.S. National Institutes of Health 1574: 1076:—can kill without spreading at all. 591:. In contrast, it is uncommon for a 484:, of which about a dozen are known. 90:Metastasis /mᵻˈtastəsɪs/ metastases 3347: 2054:The New England Journal of Medicine 1416:The New England Journal of Medicine 573: 458: 413:Although advanced cancer may cause 293:, where it represents the "M". In 24: 2659:"Cancer of Unknown Primary Origin" 2529:. New York: Taylor & Francis. 2441:Clinical and Experimental Medicine 2394:Trends in Pharmacological Sciences 1594: 431: 285:. Metastasis is a key element in 246:) tumor. Metastasis is one of the 25: 3856: 3323: 3199:Kardeh S, Kardeh B (2019-01-01). 2657:Briasoulis E, Pavlidis N (1997). 2344:International Journal of Oncology 934:sawn lengthwise, showing a large 835:fluorescent in situ hybridization 258:for example rarely metastasizes. 32:For the musical composition, see 27:Spread of a disease inside a body 1891:Cell Communication and Signaling 1238: 1224: 1050: 1038: 1026: 999: 984: 969: 943: 923: 775:cancer of unknown primary origin 553: 92: 3192: 3157: 3048: 2997: 2962: 2862: 2806: 2691: 2606: 2518: 2432: 2420: 2290: 2231: 2182: 2041: 1972: 1929: 1878: 1833: 1579:[What is metastasis?]. 1412:"Molecular basis of metastasis" 478:transforming growth factor beta 1568: 1483: 1452: 1399: 1356: 1313: 1033:Metastatic cancer in the lungs 1017:)—lower two-thirds of image). 715:in women, when it is called a 647:spreads primarily through the 13: 1: 3768:Clonally transmissible cancer 3055:López-Lázaro M (2015-01-01). 3023:10.12688/f1000research.8055.1 2676:10.1634/theoncologist.2-3-142 2207:10.1158/0008-5472.CAN-10-1142 1306: 1062: 785:", urinating blood—"probably 764:Metastasis and primary cancer 468:that make up the surrounding 3331:"Q&A: Metastatic Cancer" 3306:International Business Times 3178:10.1016/j.breast.2016.10.019 2971:Practical Radiation Oncology 2265:10.1371/journal.pone.0058183 2016:10.1371/journal.pcbi.1006395 1301:Urogenital pelvic malignancy 1295:Positron emission tomography 1197: 1072:, a cancer of the blood, or 979:of multiple liver metastases 807: 521:Endothelial progenitor cells 7: 3248:Kelland K (17 March 2014). 2928:Chronic Respiratory Disease 2067:10.1056/NEJM199101033240101 1217: 1161:, so that they can both be 1131: 955:papillary thyroid carcinoma 221:Some cancer cells known as 10: 3861: 3799:Index of oncology articles 3133:10.1038/s41598-019-45643-9 2983:10.1016/j.prro.2021.04.002 2406:10.1016/j.tips.2016.04.006 1985:PLOS Computational Biology 1750:Nature Reviews. Immunology 1168: 711:often metastasises to the 525:Inhibitor of DNA Binding 1 31: 3786: 3739: 3697: 3672: 3636: 3558: 3517: 3484: 3477: 3404: 3364: 3336:National Cancer Institute 3274:Ghosh P (18 March 2014). 2543:Angier N (3 April 2007). 2484:Cancer Metastasis Reviews 2453:10.1007/s10238-006-0117-4 1840:Yoshida BA, Sokoloff MM, 1809:10.1007/s10911-011-9217-1 1629:National Cancer Institute 1583:(in Brazilian Portuguese) 1512:10.1016/j.gde.2009.12.002 1460:"Invasion and metastasis" 1270:Collective cell migration 1191:Public Library of Science 1122:comparative effectiveness 1074:malignancies in the brain 545: 250:, distinguishing it from 147: 83: 78: 69: 61: 56: 3300:Ross P (17 March 2014). 3073:10.18632/oncoscience.159 2940:10.1177/1479972312471549 1707:Nature Reviews. Genetics 1670:10.17305/bjbms.2019.4565 659:Some tumors, especially 279:metastatic breast cancer 3721:Prostate cancer staging 3685:Paraneoplastic syndrome 2632:10.6004/jnccn.2011.0117 2146:Genes & Development 2111:10.1126/science.1150224 1863:10.1093/jnci/92.21.1717 1377:10.1126/science.1164853 1114:, are usually curable. 517:angiogenesis inhibitors 223:circulating tumor cells 3759:Tumor suppressor genes 3726:Gleason grading system 3680:Precancerous condition 3217:10.31661/gmj.v8i0.1292 2570:Nature Reviews. Cancer 1938:Nature Reviews. Cancer 1904:10.1186/1478-811X-8-23 1577:"O que é a metástase?" 1325:Merriam–Webster online 1264:Brown-Séquard syndrome 1210:, "next", and στάσις, 892:chromosome instability 817: 779:unknown primary tumors 692: 675:Organ-specific targets 623: 482:metastasis suppressors 344:, a common symptom is 317: 295:overall stage grouping 3778:Carcinogenic bacteria 3518:Malignant progression 3205:Galen Medical Journal 3004:Shahriyari L (2016). 2527:The Biology of Cancer 2356:10.3892/ijo.2017.4131 1575:Ades F (2018-07-24). 1428:10.1056/NEJMra0805239 1346:"What is Metastasis?" 1275:Contact normalization 1179:The Canon of Medicine 1006:Metastasis proven by 815: 757:pre-metastatic niches 682: 621: 613:brachiocephalic veins 365:(shortness of breath) 342:lymph node metastasis 308: 273:. This means that if 34:Metastaseis (Xenakis) 3731:Dukes classification 3356:– via YouTube. 2525:Weinberg RA (2007). 1280:Disseminated disease 994:of a lung metastasis 831:immunohistochemistry 794:immunohistochemistry 739:arise from the same 633:renal cell carcinoma 605:right lymphatic duct 495:-type movement, and 470:extracellular matrix 289:systems such as the 256:Basal cell carcinoma 36:. For the film, see 3550:Sentinel lymph node 3125:2019NatSR...9.9280S 2895:10.1038/nature25432 2887:2018Natur.553..467B 2712:1980Natur.283..139P 2316:10.4161/cc.8.3.7526 2256:2013PLoSO...858183F 2103:2008Sci...319..195G 2007:2019PLSCB..15E6395E 1472:on 20 February 2017 1371:(5897): 1785–1787. 953:of thyroid cancer ( 669:field cancerization 635:originating in the 627:Hematogenous spread 585:sentinel lymph node 513:hallmark of cancer. 248:hallmarks of cancer 196:heterogeneic tumour 3598:Respiratory system 3405:External resources 3343:on 4 January 2012. 3113:Scientific Reports 2550:The New York Times 2496:10.1007/BF00049477 2158:10.1101/gad.436307 1093:biological therapy 818: 693: 665:subarachnoid space 655:Canalicular spread 624: 424:burst, or undergo 318: 301:Signs and symptoms 291:TNM staging system 65:Metastatic disease 3827: 3826: 3814:Cancer and nausea 3693: 3692: 3530:Carcinoma in situ 3428: 3427: 2881:(7689): 467–472. 2824:(6871): 530–536. 2706:(5743): 139–146. 2625:(12): 1358–1395. 2536:978-0-8153-4076-8 2201:(18): 7273–7282. 2152:(12): 1546–1558. 2097:(5860): 195–198. 1856:(21): 1717–1730. 1561:978-0-7216-0187-8 1494:(February 2010). 1422:(26): 2814–2823. 1410:(December 2008). 1108:testicular cancer 1089:radiation therapy 930:Cut surface of a 902:. Metastases of 645:colorectal cancer 497:amoeboid movement 396:of affected bones 315:pancreatic cancer 309:Cut surface of a 210:, resulting in a 159: 158: 51:Medical condition 38:Metastases (film) 16:(Redirected from 3852: 3840:Cancer pathology 3628:Endocrine system 3593:Digestive system 3482: 3481: 3455: 3448: 3441: 3432: 3431: 3362: 3361: 3357: 3344: 3317: 3316: 3314: 3312: 3297: 3291: 3290: 3288: 3286: 3271: 3265: 3264: 3262: 3260: 3245: 3239: 3238: 3228: 3196: 3190: 3189: 3161: 3155: 3154: 3144: 3104: 3095: 3094: 3084: 3052: 3046: 3045: 3035: 3025: 3001: 2995: 2994: 2966: 2960: 2959: 2923: 2917: 2916: 2906: 2866: 2860: 2859: 2841: 2810: 2804: 2803: 2767: 2750: 2749: 2730:10.1038/283139a0 2723: 2695: 2689: 2688: 2678: 2654: 2645: 2644: 2634: 2610: 2604: 2603: 2593: 2561: 2555: 2554: 2540: 2522: 2516: 2515: 2479: 2473: 2472: 2436: 2430: 2424: 2418: 2417: 2389: 2378: 2377: 2367: 2350:(5): 1370–1382. 2335: 2329: 2328: 2318: 2294: 2288: 2287: 2277: 2267: 2235: 2229: 2228: 2218: 2186: 2180: 2179: 2169: 2137: 2131: 2130: 2086: 2080: 2079: 2069: 2045: 2039: 2038: 2028: 2018: 2000: 1976: 1970: 1969: 1933: 1927: 1926: 1916: 1906: 1882: 1876: 1875: 1865: 1837: 1831: 1830: 1820: 1788: 1782: 1781: 1745: 1739: 1738: 1698: 1692: 1691: 1681: 1649: 1640: 1639: 1637: 1636: 1621: 1592: 1591: 1589: 1588: 1581:drfelipeades.com 1572: 1566: 1565: 1547: 1534: 1533: 1523: 1487: 1481: 1480: 1478: 1477: 1465:Cancer Australia 1456: 1450: 1449: 1439: 1403: 1397: 1396: 1360: 1354: 1353: 1342: 1336: 1335: 1333: 1331: 1317: 1259:Brain metastasis 1248: 1243: 1242: 1241: 1234: 1229: 1228: 1202:Metastasis is a 1165:and metastatic. 1126:patient-centered 1054: 1042: 1030: 1003: 988: 973: 947: 927: 717:Krukenberg tumor 574:Lymphatic spread 459:Factors involved 400:Brain metastasis 369:Liver metastasis 139: 138: 135: 134: 131: 128: 124: 123: 120: 116: 115: 112: 109: 106: 102: 101: 98: 74: 54: 53: 21: 3860: 3859: 3855: 3854: 3853: 3851: 3850: 3849: 3830: 3829: 3828: 3823: 3782: 3735: 3689: 3668: 3632: 3554: 3513: 3473: 3459: 3429: 3424: 3423: 3400: 3399: 3373: 3348:Seah I, Jun Y. 3329: 3326: 3321: 3320: 3310: 3308: 3298: 3294: 3284: 3282: 3272: 3268: 3258: 3256: 3246: 3242: 3197: 3193: 3162: 3158: 3105: 3098: 3053: 3049: 3002: 2998: 2967: 2963: 2924: 2920: 2867: 2863: 2830:10.1038/415530a 2811: 2807: 2772:Nature Genetics 2768: 2753: 2721:10.1.1.553.5472 2696: 2692: 2655: 2648: 2611: 2607: 2582:10.1038/nrc3287 2562: 2558: 2537: 2523: 2519: 2480: 2476: 2437: 2433: 2425: 2421: 2390: 2381: 2336: 2332: 2295: 2291: 2236: 2232: 2195:Cancer Research 2187: 2183: 2138: 2134: 2087: 2083: 2046: 2042: 1991:(5): e1006395. 1977: 1973: 1950:10.1038/nrc1075 1934: 1930: 1883: 1879: 1838: 1834: 1789: 1785: 1762:10.1038/nri3049 1746: 1742: 1719:10.1038/nrg2101 1699: 1695: 1650: 1643: 1634: 1632: 1623: 1622: 1595: 1586: 1584: 1573: 1569: 1562: 1548: 1537: 1488: 1484: 1475: 1473: 1458: 1457: 1453: 1404: 1400: 1361: 1357: 1344: 1343: 1339: 1329: 1327: 1319: 1318: 1314: 1309: 1285:Micrometastasis 1254:Abscopal effect 1246:Medicine portal 1244: 1239: 1237: 1230: 1223: 1220: 1214:, "placement". 1200: 1171: 1150:Young's modulus 1134: 1118:Palliative care 1097:hormone therapy 1065: 1058: 1055: 1046: 1043: 1034: 1031: 1022: 1004: 995: 989: 980: 974: 965: 948: 939: 928: 912:prostate cancer 908:medulloblastoma 859:adenocarcinomas 810: 766: 701:prostate cancer 677: 657: 629: 576: 556: 548: 511:, is a crucial 461: 434: 432:Pathophysiology 390:Bone metastasis 351:Lung metastasis 346:lymphadenopathy 303: 182:cancer invasion 143: 125: 117: 103: 95: 91: 52: 49: 28: 23: 22: 15: 12: 11: 5: 3858: 3848: 3847: 3842: 3825: 3824: 3822: 3821: 3816: 3811: 3806: 3801: 3796: 3790: 3788: 3784: 3783: 3781: 3780: 3775: 3770: 3765: 3756: 3751: 3745: 3743: 3741:Carcinogenesis 3737: 3736: 3734: 3733: 3728: 3723: 3718: 3713: 3707: 3705: 3695: 3694: 3691: 3690: 3688: 3687: 3682: 3676: 3674: 3670: 3669: 3667: 3666: 3661: 3656: 3651: 3646: 3640: 3638: 3634: 3633: 3631: 3630: 3625: 3623:Nervous system 3620: 3615: 3610: 3605: 3600: 3595: 3590: 3589: 3588: 3586:nasopharyngeal 3583: 3578: 3573: 3562: 3560: 3556: 3555: 3553: 3552: 3547: 3542: 3537: 3532: 3527: 3521: 3519: 3515: 3514: 3512: 3511: 3506: 3501: 3496: 3490: 3488: 3479: 3475: 3474: 3458: 3457: 3450: 3443: 3435: 3426: 3425: 3422: 3421: 3409: 3408: 3406: 3402: 3401: 3398: 3397: 3386: 3374: 3369: 3368: 3366: 3365:Classification 3359: 3358: 3345: 3325: 3324:External links 3322: 3319: 3318: 3292: 3266: 3240: 3191: 3156: 3096: 3067:(5): 467–475. 3047: 2996: 2977:(5): 354–365. 2961: 2918: 2861: 2814:van 't Veer LJ 2805: 2784:10.1038/ng1060 2751: 2690: 2669:(3): 142–152. 2663:The Oncologist 2646: 2605: 2576:(7): 445–446. 2556: 2535: 2517: 2474: 2447:(4): 145–149. 2431: 2419: 2400:(7): 606–617. 2379: 2330: 2309:(3): 377–382. 2289: 2230: 2181: 2132: 2081: 2040: 1971: 1944:(5): 362–374. 1928: 1877: 1832: 1783: 1756:(9): 597–606. 1740: 1713:(5): 341–352. 1693: 1664:(3): 303–309. 1641: 1593: 1567: 1560: 1535: 1490:Maheswaran S, 1482: 1451: 1398: 1355: 1337: 1311: 1310: 1308: 1305: 1304: 1303: 1298: 1292: 1287: 1282: 1277: 1272: 1267: 1261: 1256: 1250: 1249: 1235: 1232:Biology portal 1219: 1216: 1199: 1196: 1170: 1167: 1163:drug-resistant 1133: 1130: 1112:thyroid cancer 1064: 1061: 1060: 1059: 1056: 1049: 1047: 1044: 1037: 1035: 1032: 1025: 1023: 1015:adenocarcinoma 1005: 998: 996: 990: 983: 981: 975: 968: 966: 949: 942: 940: 929: 922: 900:adenocarcinoma 824:For instance, 809: 806: 771:oncology units 765: 762: 709:Stomach cancer 676: 673: 656: 653: 651:to the liver. 628: 625: 575: 572: 568:ovarian tumors 555: 552: 547: 544: 460: 457: 433: 430: 411: 410: 397: 387: 366: 348: 302: 299: 287:cancer staging 202:, followed by 157: 156: 151: 145: 144: 142: 141: 87: 85: 81: 80: 76: 75: 67: 66: 63: 59: 58: 50: 26: 9: 6: 4: 3: 2: 3857: 3846: 3843: 3841: 3838: 3837: 3835: 3820: 3817: 3815: 3812: 3810: 3807: 3805: 3802: 3800: 3797: 3795: 3792: 3791: 3789: 3785: 3779: 3776: 3774: 3771: 3769: 3766: 3764: 3760: 3757: 3755: 3752: 3750: 3747: 3746: 3744: 3742: 3738: 3732: 3729: 3727: 3724: 3722: 3719: 3717: 3714: 3712: 3709: 3708: 3706: 3704: 3700: 3696: 3686: 3683: 3681: 3678: 3677: 3675: 3671: 3665: 3662: 3660: 3657: 3655: 3652: 3650: 3647: 3645: 3642: 3641: 3639: 3635: 3629: 3626: 3624: 3621: 3619: 3616: 3614: 3611: 3609: 3606: 3604: 3601: 3599: 3596: 3594: 3591: 3587: 3584: 3582: 3579: 3577: 3576:oropharyngeal 3574: 3572: 3569: 3568: 3567: 3566:Head and neck 3564: 3563: 3561: 3557: 3551: 3548: 3546: 3545:Primary tumor 3543: 3541: 3538: 3536: 3533: 3531: 3528: 3526: 3523: 3522: 3520: 3516: 3510: 3507: 3505: 3502: 3500: 3497: 3495: 3492: 3491: 3489: 3487: 3486:Benign tumors 3483: 3480: 3476: 3472: 3468: 3464: 3456: 3451: 3449: 3444: 3442: 3437: 3436: 3433: 3420: 3416: 3415: 3411: 3410: 3407: 3403: 3396: 3392: 3391: 3387: 3385: 3381: 3380: 3376: 3375: 3372: 3367: 3363: 3355: 3351: 3346: 3342: 3338: 3337: 3332: 3328: 3327: 3307: 3303: 3296: 3281: 3277: 3270: 3255: 3251: 3244: 3236: 3232: 3227: 3222: 3218: 3214: 3210: 3206: 3202: 3195: 3187: 3183: 3179: 3175: 3171: 3167: 3160: 3152: 3148: 3143: 3138: 3134: 3130: 3126: 3122: 3118: 3114: 3110: 3103: 3101: 3092: 3088: 3083: 3078: 3074: 3070: 3066: 3062: 3058: 3051: 3043: 3039: 3034: 3029: 3024: 3019: 3015: 3011: 3010:F1000Research 3007: 3000: 2992: 2988: 2984: 2980: 2976: 2972: 2965: 2957: 2953: 2949: 2945: 2941: 2937: 2933: 2929: 2922: 2914: 2910: 2905: 2900: 2896: 2892: 2888: 2884: 2880: 2876: 2872: 2865: 2857: 2853: 2849: 2845: 2840: 2835: 2831: 2827: 2823: 2819: 2815: 2809: 2801: 2797: 2793: 2789: 2785: 2781: 2777: 2773: 2766: 2764: 2762: 2760: 2758: 2756: 2747: 2743: 2739: 2735: 2731: 2727: 2722: 2717: 2713: 2709: 2705: 2701: 2694: 2686: 2682: 2677: 2672: 2668: 2664: 2660: 2653: 2651: 2642: 2638: 2633: 2628: 2624: 2620: 2616: 2609: 2601: 2597: 2592: 2587: 2583: 2579: 2575: 2571: 2567: 2560: 2552: 2551: 2546: 2538: 2532: 2528: 2521: 2513: 2509: 2505: 2501: 2497: 2493: 2489: 2485: 2478: 2470: 2466: 2462: 2458: 2454: 2450: 2446: 2442: 2435: 2429: 2423: 2415: 2411: 2407: 2403: 2399: 2395: 2388: 2386: 2384: 2375: 2371: 2366: 2361: 2357: 2353: 2349: 2345: 2341: 2334: 2326: 2322: 2317: 2312: 2308: 2304: 2300: 2293: 2285: 2281: 2276: 2271: 2266: 2261: 2257: 2253: 2250:(3): e58183. 2249: 2245: 2241: 2234: 2226: 2222: 2217: 2212: 2208: 2204: 2200: 2196: 2192: 2185: 2177: 2173: 2168: 2163: 2159: 2155: 2151: 2147: 2143: 2136: 2128: 2124: 2120: 2116: 2112: 2108: 2104: 2100: 2096: 2092: 2085: 2077: 2073: 2068: 2063: 2059: 2055: 2051: 2044: 2036: 2032: 2027: 2022: 2017: 2012: 2008: 2004: 1999: 1994: 1990: 1986: 1982: 1975: 1967: 1963: 1959: 1955: 1951: 1947: 1943: 1939: 1932: 1924: 1920: 1915: 1910: 1905: 1900: 1896: 1892: 1888: 1881: 1873: 1869: 1864: 1859: 1855: 1851: 1847: 1843: 1836: 1828: 1824: 1819: 1814: 1810: 1806: 1803:(2): 97–108. 1802: 1798: 1794: 1787: 1779: 1775: 1771: 1767: 1763: 1759: 1755: 1751: 1744: 1736: 1732: 1728: 1724: 1720: 1716: 1712: 1708: 1704: 1697: 1689: 1685: 1680: 1675: 1671: 1667: 1663: 1659: 1655: 1648: 1646: 1630: 1626: 1620: 1618: 1616: 1614: 1612: 1610: 1608: 1606: 1604: 1602: 1600: 1598: 1582: 1578: 1571: 1563: 1557: 1553: 1546: 1544: 1542: 1540: 1531: 1527: 1522: 1517: 1513: 1509: 1505: 1501: 1497: 1493: 1486: 1471: 1467: 1466: 1461: 1455: 1447: 1443: 1438: 1433: 1429: 1425: 1421: 1417: 1413: 1409: 1402: 1394: 1390: 1386: 1382: 1378: 1374: 1370: 1366: 1359: 1351: 1347: 1341: 1326: 1322: 1316: 1312: 1302: 1299: 1296: 1293: 1291: 1288: 1286: 1283: 1281: 1278: 1276: 1273: 1271: 1268: 1265: 1262: 1260: 1257: 1255: 1252: 1251: 1247: 1236: 1233: 1227: 1222: 1215: 1213: 1209: 1205: 1195: 1193: 1192: 1187: 1182: 1180: 1176: 1166: 1164: 1160: 1155: 1151: 1147: 1142: 1139: 1129: 1127: 1123: 1119: 1115: 1113: 1109: 1104: 1102: 1098: 1094: 1090: 1086: 1082: 1077: 1075: 1071: 1053: 1048: 1041: 1036: 1029: 1024: 1020: 1019:H&E stain 1016: 1012: 1009: 1002: 997: 993: 987: 982: 978: 972: 967: 964: 963:H&E stain 961:of the neck. 960: 956: 952: 946: 941: 937: 933: 926: 921: 920: 919: 915: 913: 909: 905: 904:breast cancer 901: 895: 893: 888: 884: 880: 876: 872: 868: 864: 860: 855: 850: 848: 842: 838: 836: 832: 827: 826:breast cancer 822: 814: 805: 803: 799: 795: 790: 788: 784: 780: 776: 772: 761: 758: 753: 748: 746: 742: 738: 734: 730: 726: 720: 718: 714: 710: 706: 702: 698: 697:Stephen Paget 690: 689:...metastases 686: 681: 672: 670: 666: 662: 652: 650: 646: 642: 638: 634: 620: 616: 614: 611:and into the 610: 606: 602: 601:thoracic duct 598: 594: 590: 586: 581: 571: 569: 565: 561: 554:Transcoelomic 551: 543: 539: 535: 532: 528: 526: 522: 518: 514: 510: 504: 500: 498: 494: 490: 485: 483: 479: 475: 471: 467: 456: 452: 451: 447: 443: 439: 429: 427: 423: 418: 416: 409: 405: 401: 398: 395: 392:: bone pain, 391: 388: 386: 382: 378: 374: 370: 367: 364: 360: 356: 352: 349: 347: 343: 339: 338: 337: 335: 331: 327: 323: 316: 312: 307: 298: 296: 292: 288: 284: 280: 276: 275:breast cancer 272: 271:primary tumor 268: 264: 259: 257: 253: 252:benign tumors 249: 245: 240: 236: 232: 231:blood vessels 228: 224: 219: 217: 216:tumorigenesis 213: 209: 205: 201: 197: 194: 190: 185: 183: 179: 175: 171: 167: 163: 155: 152: 150: 146: 137: 89: 88: 86: 84:Pronunciation 82: 77: 73: 68: 64: 60: 55: 47: 43: 39: 35: 30: 19: 3539: 3461:Overview of 3412: 3388: 3377: 3353: 3341:the original 3334: 3309:. Retrieved 3305: 3295: 3283:. Retrieved 3279: 3269: 3257:. Retrieved 3253: 3243: 3208: 3204: 3194: 3169: 3165: 3159: 3116: 3112: 3064: 3060: 3050: 3013: 3009: 2999: 2974: 2970: 2964: 2934:(1): 35–47. 2931: 2927: 2921: 2878: 2874: 2864: 2821: 2817: 2808: 2778:(1): 49–54. 2775: 2771: 2703: 2699: 2693: 2666: 2662: 2622: 2618: 2608: 2573: 2569: 2559: 2548: 2526: 2520: 2487: 2483: 2477: 2444: 2440: 2434: 2422: 2397: 2393: 2347: 2343: 2333: 2306: 2302: 2292: 2247: 2243: 2233: 2198: 2194: 2184: 2149: 2145: 2135: 2094: 2090: 2084: 2057: 2053: 2043: 1988: 1984: 1974: 1941: 1937: 1931: 1894: 1890: 1880: 1853: 1849: 1835: 1800: 1796: 1786: 1753: 1749: 1743: 1710: 1706: 1696: 1661: 1657: 1633:. Retrieved 1628: 1585:. Retrieved 1580: 1570: 1551: 1506:(1): 96–99. 1503: 1499: 1485: 1474:. Retrieved 1470:the original 1463: 1454: 1419: 1415: 1401: 1368: 1364: 1358: 1349: 1340: 1328:. Retrieved 1324: 1321:"Metastasis" 1315: 1211: 1207: 1201: 1189: 1183: 1172: 1143: 1135: 1116: 1105: 1085:chemotherapy 1081:radiosurgery 1078: 1066: 916: 896: 887:MHC class II 851: 843: 839: 823: 819: 791: 767: 749: 721: 705:colon cancer 694: 688: 684: 658: 630: 609:venous angle 577: 557: 549: 540: 536: 529: 509:angiogenesis 505: 501: 486: 462: 453: 435: 419: 412: 404:neurological 373:hepatomegaly 319: 282: 278: 266: 262: 260: 243: 239:hematogenous 238: 234: 220: 186: 177: 173: 161: 160: 42:Breaking Bad 41: 29: 3809:Cancer pain 3749:Cancer cell 3494:Hyperplasia 3414:MedlinePlus 3119:(1): 9280. 3061:Oncoscience 2490:(1): 5–16. 1701:Nguyen DX, 1406:Chiang AC, 1148:cells have 792:The use of 752:James Ewing 737:melanocytes 735:tissue and 649:portal vein 641:venous flow 580:lymph nodes 493:mesenchymal 422:lymph nodes 283:lung cancer 191:produces a 62:Other names 18:Metastasise 3834:Categories 3754:Carcinogen 3618:Urogenital 3559:Topography 3540:Metastasis 3504:Pseudocyst 3478:Conditions 3390:DiseasesDB 2839:1874/15552 2541:quoted in 2303:Cell Cycle 2060:(1): 1–8. 1998:1811.09326 1703:Massagué J 1635:2008-11-01 1587:2018-10-23 1476:2018-10-26 1408:Massagué J 1350:Cancer.Net 1307:References 1154:elasticity 1138:hypothesis 1063:Management 959:lymph node 951:Micrograph 661:carcinomas 589:carcinomas 560:peritoneal 531:Epigenetic 474:chemokines 448:, and the 375:(enlarged 359:hemoptysis 267:metastatic 200:metaplasia 174:metastases 166:pathogenic 162:Metastasis 57:Metastasis 46:Metástasis 3773:Oncovirus 3763:oncogenes 3716:Ann Arbor 3659:Papilloma 3644:Carcinoma 3637:Histology 3581:laryngeal 3525:Dysplasia 3509:Hamartoma 3211:: e1292. 3172:: 20–21. 2716:CiteSeerX 1897:(1): 23. 1393:206515808 1330:20 August 1198:Etymology 1194:journal. 936:cancerous 808:Diagnosis 777:(CUP) or 750:In 1928, 741:cell line 685:...cancer 263:secondary 244:secondary 235:lymphatic 227:lymphatic 212:malignant 208:anaplasia 204:dysplasia 170:cancerous 149:Specialty 3845:Oncology 3794:Research 3654:Blastoma 3471:oncology 3311:18 March 3285:18 March 3259:18 March 3235:34466487 3186:27810694 3151:31243305 3091:26097879 3042:27158448 2991:34119447 2948:23355404 2913:29342134 2848:11823860 2800:12059602 2792:12469122 2685:10388044 2641:22157556 2600:22912952 2512:19573769 2469:26736196 2461:17191105 2414:27157716 2374:29048609 2325:19177007 2284:23520493 2244:PLOS ONE 2225:20807818 2176:17575055 2127:12577022 2119:18187653 2035:31048903 1958:12724734 1923:20822528 1872:11058615 1842:Welch DR 1827:21494783 1778:34438005 1770:21866172 1735:17745552 1727:17440531 1688:32020846 1530:20071161 1492:Haber DA 1446:19109576 1385:18818347 1218:See also 1175:Ibn Sina 1146:melanoma 1132:Research 1070:leukemia 1013:(tumor ( 992:CT image 977:CT image 833:, FISH ( 798:melanoma 729:melanoma 489:motility 466:proteins 394:fracture 385:jaundice 154:Oncology 3804:History 3703:grading 3699:Staging 3664:Adenoma 3649:Sarcoma 3384:D009362 3254:Reuters 3226:8344088 3142:6594928 3121:Bibcode 3082:4468332 3033:4847566 3016:: 175. 2956:6743524 2904:5785464 2883:Bibcode 2856:4369266 2746:4302076 2738:6985715 2708:Bibcode 2591:4533867 2504:6764375 2365:5642393 2275:3592916 2252:Bibcode 2216:3058751 2167:1891431 2099:Bibcode 2091:Science 2076:1701519 2026:6497229 2003:Bibcode 1966:5547981 1914:2941746 1818:3095797 1679:7416172 1521:2846729 1437:4189180 1365:Science 1169:History 1101:surgery 957:) in a 932:humerus 875:securin 854:somatic 802:autopsy 787:bladder 743:in the 597:outcome 593:sarcoma 564:pleural 408:vertigo 363:dyspnea 193:primary 189:mitosis 3535:Cancer 3467:cancer 3463:tumors 3419:002260 3354:TED-Ed 3233: 3223: 3184: 3166:Breast 3149: 3139: 3089: 3079: 3040: 3030: 2989: 2954: 2946: 2911: 2901: 2875:Nature 2854: 2846: 2818:Nature 2798: 2790: 2744: 2736: 2718: 2700:Nature 2683: 2639: 2598: 2588: 2533: 2510: 2502: 2467: 2459: 2412: 2372: 2362: 2323: 2282: 2272: 2223: 2213: 2174: 2164: 2125: 2117: 2074: 2033: 2023: 1964: 1956: 1921: 1911: 1870: 1825: 1815: 1776: 1768: 1733: 1725: 1686: 1676: 1558: 1528: 1518: 1444: 1434: 1391: 1383: 1212:stasis 1159:tumors 1011:biopsy 883:myosin 867:HNRPAB 847:biopsy 745:embryo 733:neural 637:kidney 546:Routes 381:nausea 332:, and 281:, not 140: 44:, see 3787:Misc. 3673:Other 3613:Blood 3395:28954 2952:S2CID 2852:S2CID 2796:S2CID 2742:S2CID 2508:S2CID 2465:S2CID 2123:S2CID 1993:arXiv 1962:S2CID 1774:S2CID 1731:S2CID 1389:S2CID 1297:(PET) 1204:Greek 1186:Sudan 1008:liver 879:Actin 863:SNRPF 713:ovary 450:bones 446:brain 442:liver 438:lungs 426:lysis 377:liver 355:cough 334:bones 330:brain 326:liver 322:lungs 311:liver 206:then 164:is a 3819:Diet 3608:Skin 3603:Bone 3571:oral 3499:Cyst 3469:and 3379:MeSH 3313:2014 3287:2014 3261:2014 3231:PMID 3182:PMID 3147:PMID 3087:PMID 3038:PMID 2987:PMID 2944:PMID 2909:PMID 2844:PMID 2788:PMID 2734:PMID 2681:PMID 2637:PMID 2596:PMID 2531:ISBN 2500:PMID 2457:PMID 2410:PMID 2370:PMID 2321:PMID 2280:PMID 2221:PMID 2172:PMID 2115:PMID 2072:PMID 2031:PMID 1954:PMID 1919:PMID 1868:PMID 1823:PMID 1766:PMID 1723:PMID 1684:PMID 1556:ISBN 1526:PMID 1442:PMID 1381:PMID 1332:2017 1208:meta 1124:and 1110:and 910:and 885:and 873:and 871:DHPS 852:The 783:lung 725:ions 603:and 476:and 415:pain 383:and 361:and 178:mets 3711:TNM 3280:BBC 3221:PMC 3213:doi 3174:doi 3137:PMC 3129:doi 3077:PMC 3069:doi 3028:PMC 3018:doi 2979:doi 2936:doi 2899:PMC 2891:doi 2879:553 2834:hdl 2826:doi 2822:415 2780:doi 2726:doi 2704:283 2671:doi 2627:doi 2586:PMC 2578:doi 2492:doi 2449:doi 2402:doi 2360:PMC 2352:doi 2311:doi 2270:PMC 2260:doi 2211:PMC 2203:doi 2162:PMC 2154:doi 2107:doi 2095:319 2062:doi 2058:324 2021:PMC 2011:doi 1946:doi 1909:PMC 1899:doi 1858:doi 1813:PMC 1805:doi 1758:doi 1715:doi 1674:PMC 1666:doi 1516:PMC 1508:doi 1432:PMC 1424:doi 1420:359 1373:doi 1369:321 877:. 671:). 379:), 340:In 265:or 237:or 229:or 3836:: 3465:, 3417:: 3393:: 3382:: 3352:. 3333:. 3304:. 3278:. 3252:. 3229:. 3219:. 3207:. 3203:. 3180:. 3170:31 3168:. 3145:. 3135:. 3127:. 3115:. 3111:. 3099:^ 3085:. 3075:. 3063:. 3059:. 3036:. 3026:. 3012:. 3008:. 2985:. 2975:11 2973:. 2950:. 2942:. 2932:10 2930:. 2907:. 2897:. 2889:. 2877:. 2873:. 2850:. 2842:. 2832:. 2820:. 2794:. 2786:. 2776:33 2774:. 2754:^ 2740:. 2732:. 2724:. 2714:. 2702:. 2679:. 2665:. 2661:. 2649:^ 2635:. 2621:. 2617:. 2594:. 2584:. 2574:12 2572:. 2568:. 2547:. 2506:. 2498:. 2486:. 2463:. 2455:. 2443:. 2408:. 2398:37 2396:. 2382:^ 2368:. 2358:. 2348:51 2346:. 2342:. 2319:. 2305:. 2301:. 2278:. 2268:. 2258:. 2246:. 2242:. 2219:. 2209:. 2199:70 2197:. 2193:. 2170:. 2160:. 2150:21 2148:. 2144:. 2121:. 2113:. 2105:. 2093:. 2070:. 2056:. 2052:. 2029:. 2019:. 2009:. 2001:. 1989:15 1987:. 1983:. 1960:. 1952:. 1940:. 1917:. 1907:. 1893:. 1889:. 1866:. 1854:92 1852:. 1848:. 1821:. 1811:. 1801:16 1799:. 1795:. 1772:. 1764:. 1754:11 1752:. 1729:. 1721:. 1709:. 1682:. 1672:. 1662:20 1660:. 1656:. 1644:^ 1627:. 1596:^ 1538:^ 1524:. 1514:. 1504:20 1502:. 1498:. 1462:. 1440:. 1430:. 1418:. 1414:. 1387:. 1379:. 1367:. 1348:. 1323:. 1099:, 1095:, 1091:, 1087:, 1083:, 906:, 881:, 869:, 865:, 747:. 719:. 691:". 562:, 491:, 444:, 440:, 428:. 402:: 371:: 357:, 353:: 328:, 324:, 218:. 130:iː 3761:/ 3701:/ 3454:e 3447:t 3440:v 3371:D 3315:. 3289:. 3263:. 3237:. 3215:: 3209:8 3188:. 3176:: 3153:. 3131:: 3123:: 3117:9 3093:. 3071:: 3065:2 3044:. 3020:: 3014:5 2993:. 2981:: 2958:. 2938:: 2915:. 2893:: 2885:: 2858:. 2836:: 2828:: 2802:. 2782:: 2748:. 2728:: 2710:: 2687:. 2673:: 2667:2 2643:. 2629:: 2623:9 2602:. 2580:: 2553:. 2539:. 2514:. 2494:: 2488:1 2471:. 2451:: 2445:6 2416:. 2404:: 2376:. 2354:: 2327:. 2313:: 2307:8 2286:. 2262:: 2254:: 2248:8 2227:. 2205:: 2178:. 2156:: 2129:. 2109:: 2101:: 2078:. 2064:: 2037:. 2013:: 2005:: 1995:: 1968:. 1948:: 1942:3 1925:. 1901:: 1895:8 1874:. 1860:: 1829:. 1807:: 1780:. 1760:: 1737:. 1717:: 1711:8 1690:. 1668:: 1638:. 1590:. 1564:. 1532:. 1510:: 1479:. 1448:. 1426:: 1395:. 1375:: 1334:. 1021:. 176:( 136:/ 133:z 127:s 122:ə 119:t 114:s 111:æ 108:t 105:ˈ 100:ə 97:m 94:/ 48:. 20:)

Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.