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Hallmarks of Metastasis: Molecular Underpinnings

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Cancer Metastasis Through the Lymphovascular System

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Abstract

Metastasis is one of the most important hallmarks in cancer biology responsible for the majority of cancer-related deaths in patients. Cancer cells undergo a series of processes orchestrated by genetic changes in order to acquire invasive properties that allow them to migrate to secondary sites and become a metastatic focus. In this chapter, we will review the molecular bases of the most relevant steps in metastasis, including invasion, intravasation, circulation, extravasation, and metastatic colonization.

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References

  1. Luzzi KJ, MacDonald IC, Schmidt EE, Kerkvliet N, Morris VL, Chambers AF, Groom AC. Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am J Pathol. 1998;153(3):865–73. https://doi.org/10.1016/S0002-9440(10)65628-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol. 2019;20(2):69–84. https://doi.org/10.1038/s41580-018-0080-4.

    Article  CAS  PubMed  Google Scholar 

  3. Fares J, Fares MY, Khachfe HH, Salhab HA, Fares Y. Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduct Target Ther. 2020;5(1):28. https://doi.org/10.1038/s41392-020-0134-x.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Tam WL, Weinberg RA. The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat Med. 2013;19(11):1438–49. https://doi.org/10.1038/nm.3336.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cano A, Perez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, Portillo F, Nieto MA. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000;2(2):76–83. https://doi.org/10.1038/35000025.

    Article  CAS  PubMed  Google Scholar 

  6. Herranz N, Pasini D, Diaz VM, Franci C, Gutierrez A, Dave N, Escriva M, Hernandez-Munoz I, Di Croce L, Helin K, Garcia de Herreros A, Peiro S. Polycomb complex 2 is required for E-cadherin repression by the Snail1 transcription factor. Mol Cell Biol. 2008;28(15):4772–81. https://doi.org/10.1128/MCB.00323-08.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sanchez-Tillo E, Lazaro A, Torrent R, Cuatrecasas M, Vaquero EC, Castells A, Engel P, Postigo A. ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatin-remodeling protein BRG1. Oncogene. 2010;29(24):3490–500. https://doi.org/10.1038/onc.2010.102.

    Article  CAS  PubMed  Google Scholar 

  8. Spaderna S, Schmalhofer O, Wahlbuhl M, Dimmler A, Bauer K, Sultan A, Hlubek F, Jung A, Strand D, Eger A, Kirchner T, Behrens J, Brabletz T. The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer. Cancer Res. 2008;68(2):537–44. https://doi.org/10.1158/0008-5472.CAN-07-5682.

    Article  CAS  PubMed  Google Scholar 

  9. Miyoshi A, Kitajima Y, Kido S, Shimonishi T, Matsuyama S, Kitahara K, Miyazaki K. Snail accelerates cancer invasion by upregulating MMP expression and is associated with poor prognosis of hepatocellular carcinoma. Br J Cancer. 2005;92(2):252–8. https://doi.org/10.1038/sj.bjc.6602266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Miyoshi A, Kitajima Y, Sumi K, Sato K, Hagiwara A, Koga Y, Miyazaki K. Snail and SIP1 increase cancer invasion by upregulating MMP family in hepatocellular carcinoma cells. Br J Cancer. 2004;90(6):1265–73. https://doi.org/10.1038/sj.bjc.6601685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Toh B, Wang X, Keeble J, Sim WJ, Khoo K, Wong WC, Kato M, Prevost-Blondel A, Thiery JP, Abastado JP. Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor. PLoS Biol. 2011;9(9):e1001162. https://doi.org/10.1371/journal.pbio.1001162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Goebel L, Grage-Griebenow E, Gorys A, Helm O, Genrich G, Lenk L, Wesch D, Ungefroren H, Freitag-Wolf S, Sipos B, Rocken C, Schafer H, Sebens S. CD4(+) T cells potently induce epithelial-mesenchymal-transition in premalignant and malignant pancreatic ductal epithelial cells-novel implications of CD4(+) T cells in pancreatic cancer development. Onco Targets Ther. 2015;4(4):e1000083. https://doi.org/10.1080/2162402X.2014.1000083.

    Article  CAS  Google Scholar 

  13. Cohen EN, Gao H, Anfossi S, Mego M, Reddy NG, Debeb B, Giordano A, Tin S, Wu Q, Garza RJ, Cristofanilli M, Mani SA, Croix DA, Ueno NT, Woodward WA, Luthra R, Krishnamurthy S, Reuben JM. Inflammation mediated metastasis: immune induced epithelial-to-mesenchymal transition in inflammatory breast cancer cells. PLoS One. 2015;10(7):e0132710. https://doi.org/10.1371/journal.pone.0132710.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene. 2010;29(34):4741–51. https://doi.org/10.1038/onc.2010.215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kudo-Saito C, Shirako H, Takeuchi T, Kawakami Y. Cancer metastasis is accelerated through immunosuppression during snail-induced EMT of cancer cells. Cancer Cell. 2009;15(3):195–206. https://doi.org/10.1016/j.ccr.2009.01.023.

    Article  CAS  PubMed  Google Scholar 

  16. Fischer KR, Durrans A, Lee S, Sheng J, Li F, Wong ST, Choi H, El Rayes T, Ryu S, Troeger J, Schwabe RF, Vahdat LT, Altorki NK, Mittal V, Gao D. Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature. 2015;527(7579):472–6. https://doi.org/10.1038/nature15748.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zheng X, Carstens JL, Kim J, Scheible M, Kaye J, Sugimoto H, Wu CC, LeBleu VS, Kalluri R. Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature. 2015;527(7579):525–30. https://doi.org/10.1038/nature16064.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lambert AW, Pattabiraman DR, Weinberg RA. Emerging biological principles of metastasis. Cell. 2017;168(4):670–91. https://doi.org/10.1016/j.cell.2016.11.037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Freedland SJ, Aronson WJ. Commentary on “Integrative clinical genomics of advanced prostate cancer”. Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, Montgomery B, Taplin ME, Pritchard CC, Attard G, Beltran H, Abida W, Bradley RK, Vinson J, Cao X, Vats P, Kunju LP, Hussain M, Feng FY, Tomlins SA, Cooney KA, Smith DC, Brennan C, Siddiqui J, Mehra R, Chen Y, Rathkopf DE, Morris MJ, Solomon SB, Durack JC, Reuter VE, Gopalan A, Gao J, Loda M, Lis RT, Bowden M, Balk SP, Gaviola G, Sougnez C, Gupta M, Yu EY, Mostaghel EA, Cheng HH, Mulcahy H, True LD, Plymate SR, Dvinge H, Ferraldeschi R, Flohr P, Miranda S, Zafeiriou Z, Tunariu N, Mateo J, Perez-Lopez R, Demichelis F, Robinson BD, Schiffman M, Nanus DM, Tagawa ST, Sigaras A, Eng KW, Elemento O, Sboner A, Heath EI, Scher HI, Pienta KJ, Kantoff P, de Bono JS, Rubin MA, Nelson PS, Garraway LA, Sawyers CL, Chinnaiyan AM. Cell. 21 May 2015;161(5):1215–1228. Urol Oncol. 2017;35(8):535. https://doi.org/10.1016/j.urolonc.2017.05.010.

    Article  CAS  PubMed  Google Scholar 

  20. Rankin EB, Giaccia AJ. Hypoxic control of metastasis. Science. 2016;352(6282):175–80. https://doi.org/10.1126/science.aaf4405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 2007;26(2):225–39. https://doi.org/10.1007/s10555-007-9055-1.

    Article  CAS  PubMed  Google Scholar 

  22. Rankin EB, Fuh KC, Castellini L, Viswanathan K, Finger EC, Diep AN, LaGory EL, Kariolis MS, Chan A, Lindgren D, Axelson H, Miao YR, Krieg AJ, Giaccia AJ. Direct regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET. Proc Natl Acad Sci U S A. 2014;111(37):13373–8. https://doi.org/10.1073/pnas.1404848111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Semenza GL. Cancer-stromal cell interactions mediated by hypoxia-inducible factors promote angiogenesis, lymphangiogenesis, and metastasis. Oncogene. 2013;32(35):4057–63. https://doi.org/10.1038/onc.2012.578.

    Article  CAS  PubMed  Google Scholar 

  24. Noman MZ, Messai Y, Muret J, Hasmim M, Chouaib S. Crosstalk between CTC, immune system and hypoxic tumor microenvironment. Cancer Microenviron. 2014;7(3):153–60. https://doi.org/10.1007/s12307-014-0157-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Harney AS, Arwert EN, Entenberg D, Wang Y, Guo P, Qian BZ, Oktay MH, Pollard JW, Jones JG, Condeelis JS. Real-time imaging reveals local, transient vascular permeability, and tumor cell Intravasation stimulated by TIE2hi macrophage-derived VEGFA. Cancer Discov. 2015;5(9):932–43. https://doi.org/10.1158/2159-8290.CD-15-0012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Roussos ET, Condeelis JS, Patsialou A. Chemotaxis in cancer. Nat Rev Cancer. 2011;11(8):573–87. https://doi.org/10.1038/nrc3078.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zervantonakis IK, Hughes-Alford SK, Charest JL, Condeelis JS, Gertler FB, Kamm RD. Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function. Proc Natl Acad Sci U S A. 2012;109(34):13515–20. https://doi.org/10.1073/pnas.1210182109.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Wong AD, Searson PC. Mitosis-mediated intravasation in a tissue-engineered tumor-microvessel platform. Cancer Res. 2017;77(22):6453–61. https://doi.org/10.1158/0008-5472.CAN-16-3279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Friedl P, Wolf K. Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer. 2003;3(5):362–74. https://doi.org/10.1038/nrc1075.

    Article  CAS  PubMed  Google Scholar 

  30. Alitalo K, Carmeliet P. Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cell. 2002;1(3):219–27. https://doi.org/10.1016/s1535-6108(02)00051-x.

    Article  CAS  PubMed  Google Scholar 

  31. Wong SY, Hynes RO. Lymphatic or hematogenous dissemination: how does a metastatic tumor cell decide? Cell Cycle. 2006;5(8):812–7. https://doi.org/10.4161/cc.5.8.2646.

    Article  CAS  PubMed  Google Scholar 

  32. Aleskandarany MA, Sonbul SN, Mukherjee A, Rakha EA. Molecular mechanisms underlying lymphovascular invasion in invasive breast cancer. Pathobiology. 2015;82(3–4):113–23. https://doi.org/10.1159/000433583.

    Article  CAS  PubMed  Google Scholar 

  33. Dadiani M, Kalchenko V, Yosepovich A, Margalit R, Hassid Y, Degani H, Seger D. Real-time imaging of lymphogenic metastasis in orthotopic human breast cancer. Cancer Res. 2006;66(16):8037–41. https://doi.org/10.1158/0008-5472.CAN-06-0728.

    Article  CAS  PubMed  Google Scholar 

  34. Ran S, Volk L, Hall K, Flister MJ. Lymphangiogenesis and lymphatic metastasis in breast cancer. Pathophysiology. 2010;17(4):229–51. https://doi.org/10.1016/j.pathophys.2009.11.003.

    Article  PubMed  Google Scholar 

  35. LeBedis C, Chen K, Fallavollita L, Boutros T, Brodt P. Peripheral lymph node stromal cells can promote growth and tumorigenicity of breast carcinoma cells through the release of IGF-I and EGF. Int J Cancer. 2002;100(1):2–8. https://doi.org/10.1002/ijc.10481.

    Article  CAS  PubMed  Google Scholar 

  36. Schoppmann SF, Birner P, Stockl J, Kalt R, Ullrich R, Caucig C, Kriehuber E, Nagy K, Alitalo K, Kerjaschki D. Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. Am J Pathol. 2002;161(3):947–56. https://doi.org/10.1016/S0002-9440(10)64255-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Das S, Sarrou E, Podgrabinska S, Cassella M, Mungamuri SK, Feirt N, Gordon R, Nagi CS, Wang Y, Entenberg D, Condeelis J, Skobe M. Tumor cell entry into the lymph node is controlled by CCL1 chemokine expressed by lymph node lymphatic sinuses. J Exp Med. 2013;210(8):1509–28. https://doi.org/10.1084/jem.20111627.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Homey B, Muller A, Zlotnik A. Chemokines: agents for the immunotherapy of cancer? Nat Rev Immunol. 2002;2(3):175–84. https://doi.org/10.1038/nri748.

    Article  CAS  PubMed  Google Scholar 

  39. Korbecki J, Grochans S, Gutowska I, Barczak K, Baranowska-Bosiacka I. CC chemokines in a tumor: a review of pro-cancer and anti-cancer properties of receptors CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 ligands. Int J Mol Sci. 2020;21(20) https://doi.org/10.3390/ijms21207619.

  40. Wiley HE, Gonzalez EB, Maki W, Wu MT, Hwang ST. Expression of CC chemokine receptor-7 and regional lymph node metastasis of B16 murine melanoma. J Natl Cancer Inst. 2001;93(21):1638–43. https://doi.org/10.1093/jnci/93.21.1638.

    Article  CAS  PubMed  Google Scholar 

  41. Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, Yu M, Pely A, Engstrom A, Zhu H, Brannigan BW, Kapur R, Stott SL, Shioda T, Ramaswamy S, Ting DT, Lin CP, Toner M, Haber DA, Maheswaran S. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell. 2014;158(5):1110–22. https://doi.org/10.1016/j.cell.2014.07.013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Labelle M, Begum S, Hynes RO. Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell. 2011;20(5):576–90. https://doi.org/10.1016/j.ccr.2011.09.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Granot Z, Henke E, Comen EA, King TA, Norton L, Benezra R. Tumor entrained neutrophils inhibit seeding in the premetastatic lung. Cancer Cell. 2011;20(3):300–14. https://doi.org/10.1016/j.ccr.2011.08.012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Szczerba BM, Castro-Giner F, Vetter M, Krol I, Gkountela S, Landin J, Scheidmann MC, Donato C, Scherrer R, Singer J, Beisel C, Kurzeder C, Heinzelmann-Schwarz V, Rochlitz C, Weber WP, Beerenwinkel N, Aceto N. Neutrophils escort circulating tumour cells to enable cell cycle progression. Nature. 2019;566(7745):553–7. https://doi.org/10.1038/s41586-019-0915-y.

    Article  CAS  PubMed  Google Scholar 

  45. Welch DR, Hurst DR. Defining the hallmarks of metastasis. Cancer Res. 2019;79(12):3011–27. https://doi.org/10.1158/0008-5472.CAN-19-0458.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, Kaiser EA, Snyder LA, Pollard JW. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature. 2011;475(7355):222–5. https://doi.org/10.1038/nature10138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Wolf MJ, Hoos A, Bauer J, Boettcher S, Knust M, Weber A, Simonavicius N, Schneider C, Lang M, Sturzl M, Croner RS, Konrad A, Manz MG, Moch H, Aguzzi A, van Loo G, Pasparakis M, Prinz M, Borsig L, Heikenwalder M. Endothelial CCR2 signaling induced by colon carcinoma cells enables extravasation via the JAK2-Stat5 and p38MAPK pathway. Cancer Cell. 2012;22(1):91–105. https://doi.org/10.1016/j.ccr.2012.05.023.

    Article  CAS  PubMed  Google Scholar 

  48. Giancotti FG. Mechanisms governing metastatic dormancy and reactivation. Cell. 2013;155(4):750–64. https://doi.org/10.1016/j.cell.2013.10.029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Zhang XH, Wang Q, Gerald W, Hudis CA, Norton L, Smid M, Foekens JA, Massague J. Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell. 2009;16(1):67–78. https://doi.org/10.1016/j.ccr.2009.05.017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. El Touny LH, Vieira A, Mendoza A, Khanna C, Hoenerhoff MJ, Green JE. Combined SFK/MEK inhibition prevents metastatic outgrowth of dormant tumor cells. J Clin Invest. 2014;124(1):156–68. https://doi.org/10.1172/JCI70259.

    Article  CAS  PubMed  Google Scholar 

  51. Yeh AC, Ramaswamy S. Mechanisms of cancer cell dormancy—another Hallmark of cancer? Cancer Res. 2015;75(23):5014–22. https://doi.org/10.1158/0008-5472.CAN-15-1370.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kobayashi A, Okuda H, Xing F, Pandey PR, Watabe M, Hirota S, Pai SK, Liu W, Fukuda K, Chambers C, Wilber A, Watabe K. Bone morphogenetic protein 7 in dormancy and metastasis of prostate cancer stem-like cells in bone. J Exp Med. 2011;208(13):2641–55. https://doi.org/10.1084/jem.20110840.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Sosa MS, Avivar-Valderas A, Bragado P, Wen HC, Aguirre-Ghiso JA. ERK1/2 and p38alpha/beta signaling in tumor cell quiescence: opportunities to control dormant residual disease. Clin Cancer Res. 2011;17(18):5850–7. https://doi.org/10.1158/1078-0432.CCR-10-2574.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Shiozawa Y, Pedersen EA, Havens AM, Jung Y, Mishra A, Joseph J, Kim JK, Patel LR, Ying C, Ziegler AM, Pienta MJ, Song J, Wang J, Loberg RD, Krebsbach PH, Pienta KJ, Taichman RS. Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J Clin Invest. 2011;121(4):1298–312. https://doi.org/10.1172/JCI43414.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Cedervall J, Zhang Y, Olsson AK. Tumor-induced NETosis as a risk factor for metastasis and organ failure. Cancer Res. 2016;76(15):4311–5. https://doi.org/10.1158/0008-5472.CAN-15-3051.

    Article  CAS  PubMed  Google Scholar 

  56. Zomer A, Maynard C, Verweij FJ, Kamermans A, Schafer R, Beerling E, Schiffelers RM, de Wit E, Berenguer J, Ellenbroek SIJ, Wurdinger T, Pegtel DM, van Rheenen J. In vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior. Cell. 2015;161(5):1046–57. https://doi.org/10.1016/j.cell.2015.04.042.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Tarbe N, Losch S, Burtscher H, Jarsch M, Weidle UH. Identification of rat pancreatic carcinoma genes associated with lymphogenous metastasis. Anticancer Res. 2002;22(4):2015–27.

    CAS  PubMed  Google Scholar 

  58. Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, Molina H, Kohsaka S, Di Giannatale A, Ceder S, Singh S, Williams C, Soplop N, Uryu K, Pharmer L, King T, Bojmar L, Davies AE, Ararso Y, Zhang T, Zhang H, Hernandez J, Weiss JM, Dumont-Cole VD, Kramer K, Wexler LH, Narendran A, Schwartz GK, Healey JH, Sandstrom P, Labori KJ, Kure EH, Grandgenett PM, Hollingsworth MA, de Sousa M, Kaur S, Jain M, Mallya K, Batra SK, Jarnagin WR, Brady MS, Fodstad O, Muller V, Pantel K, Minn AJ, Bissell MJ, Garcia BA, Kang Y, Rajasekhar VK, Ghajar CM, Matei I, Peinado H, Bromberg J, Lyden D. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527(7578):329–35. https://doi.org/10.1038/nature15756.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, MI, USA

    Juan C. Gomez-Gelvez & Dhananjay A. Chitale

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  1. Juan C. Gomez-Gelvez
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  2. Dhananjay A. Chitale
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Correspondence to Juan C. Gomez-Gelvez .

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  1. Department of Surgery and Melanoma Center, California Pacific Medical Center and Research Institute, San Francisco, CA, USA

    Stanley P. Leong

  2. Henry Ford Cancer Institute, Detroit, MI, USA

    S. David Nathanson

  3. Moffitt Cancer Center, Tampa, FL, USA

    Jonathan S. Zager

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Gomez-Gelvez, J.C., Chitale, D.A. (2022). Hallmarks of Metastasis: Molecular Underpinnings. In: Leong, S.P., Nathanson, S.D., Zager, J.S. (eds) Cancer Metastasis Through the Lymphovascular System. Springer, Cham. https://doi.org/10.1007/978-3-030-93084-4_4

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