Pathophysiology of Tumor Cell Release into the Circulation and Characterization of CTC

  • Tilman Todenhöfer
  • Klaus PantelEmail author
  • Arnulf Stenzl
  • Stefan Werner
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 215)


The traditional model of metastatic progression postulates that the ability to form distant metastases is driven by random mutations in cells of the primary tumor.


  1. Aktas B, Tewes M, Fehm T, Hauch S, Kimmig R, Kasimir-Bauer S (2009) Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res 11(4):R46. Scholar
  2. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 100(7):3983–3988. Scholar
  3. Alix-Panabieres C, Pantel K (2014) Technologies for detection of circulating tumor cells: facts and vision. Lab Chip 14(1):57–62. Scholar
  4. Alix-Panabieres C, Pantel K (2016) Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov 6(5):479–491. Scholar
  5. Alix-Panabieres C, Bartkowiak K, Pantel K (2016) Functional studies on circulating and disseminated tumor cells in carcinoma patients. Mol Oncol 10(3):443–449. Scholar
  6. Alonso-Alconada L, Muinelo-Romay L, Madissoo K, Diaz-Lopez A, Krakstad C, Trovik J et al (2014) Molecular profiling of circulating tumor cells links plasticity to the metastatic process in endometrial cancer. Mol Cancer 13:223. Scholar
  7. Andreopoulou E, Yang LY, Rangel KM, Reuben JM, Hsu L, Krishnamurthy S et al (2012) Comparison of assay methods for detection of circulating tumor cells in metastatic breast cancer: AdnaGen AdnaTest BreastCancer Select/Detect versus Veridex Cell Search system. Int J Cancer 130(7):1590–1597. Scholar
  8. Armstrong AJ, Marengo MS, Oltean S, Kemeny G, Bitting RL, Turnbull JD et al (2011) Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Mol Cancer Res 9(8):997–1007. Scholar
  9. Baccelli I, Schneeweiss A, Riethdorf S, Stenzinger A, Schillert A, Vogel V et al (2013) Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol 31(6):539–544. Scholar
  10. Barber AG, Castillo-Martin M, Bonal DM, Jia AJ, Rybicki BA, Christiano AM et al (2015) PI3K/AKT pathway regulates E-cadherin and Desmoglein 2 in aggressive prostate cancer. Cancer Med 4(8):1258–1271. Scholar
  11. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M et al (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449(7165):1003–1007. Scholar
  12. Barriere G, Fici P, Gallerani G, Fabbri F, Zoli W, Rigaud M (2014) Circulating tumor cells and epithelial, mesenchymal and stemness markers: characterization of cell subpopulations. Ann Transl Med 2(11):109. Scholar
  13. Bock C, Rack B, Huober J, Andergassen U, Jeschke U, Doisneau-Sixou S (2014) Distinct expression of cytokeratin, N-cadherin and CD133 in circulating tumor cells of metastatic breast cancer patients. Future Oncol 10(10):1751–1765. Scholar
  14. Bourcy M, Suarez-Carmona M, Lambert J, Francart ME, Schroeder H, Delierneux C et al (2016) Tissue factor induced by epithelial-mesenchymal transition triggers a procoagulant state that drives metastasis of circulating tumor cells. Cancer Res 76(14):4270–4282. Scholar
  15. Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC et al (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353(8):793–802. Scholar
  16. Cannito S, Novo E, Compagnone A, Valfre di Bonzo L, Busletta C, Zamara E et al (2008) Redox mechanisms switch on hypoxia-dependent epithelial-mesenchymal transition in cancer cells. Carcinogenesis. 29(12):2267–2278. Scholar
  17. Cayrefourcq L, Mazard T, Joosse S, Solassol J, Ramos J, Assenat E et al (2015) Establishment and characterization of a cell line from human circulating colon cancer cells. Cancer Res 75(5):892–901. Scholar
  18. Celia-Terrassa T, Kang Y (2016) Distinctive properties of metastasis-initiating cells. Genes Dev 30(8):892–908. Scholar
  19. Chang K, Kong YY, Dai B, Ye DW, Qu YY, Wang Y et al (2015) Combination of circulating tumor cell enumeration and tumor marker detection in predicting prognosis and treatment effect in metastatic castration-resistant prostate cancer. Oncotarget 6(39):41825–41836. Scholar
  20. Clevers H (2011) The cancer stem cell: premises, promises and challenges. Nat Med 17(3):313–319. Scholar
  21. Coumans FA, Siesling S, Terstappen LW (2013) Detection of cancer before distant metastasis. BMC Cancer 13:283. Scholar
  22. De Craene B, Berx G (2013) Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer 13(2):97–110. Scholar
  23. Dinney CPN, Melnikova VO, Pretzsch SM, Garza M, Wu W, Davis DW et al (2014) Heterogeneity of circulating tumor cells isolated from bladder cancer patients using ApoStream and biomarkers of epithelial-mesenchymal transition. J Clin Oncol 32(4_suppl):349. Scholar
  24. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61(5):759–767CrossRefGoogle Scholar
  25. Fidler IJ, Kripke ML (1977) Metastasis results from preexisting variant cells within a malignant tumor. Science 197(4306):893–895CrossRefGoogle Scholar
  26. Finlay J, Roberts CM, Lowe G, Loeza J, Rossi JJ, Glackin CA (2015) RNA-based TWIST1 inhibition via dendrimer complex to reduce breast cancer cell metastasis. Biomed Res Int 2015:382745. Scholar
  27. Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S et al (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64(19):7011–7021. Scholar
  28. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M et al (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1(5):555–567. Scholar
  29. Giordano A, Gao H, Anfossi S, Cohen E, Mego M, Lee BN et al (2012) Epithelial-mesenchymal transition and stem cell markers in patients with HER2-positive metastatic breast cancer. Mol Cancer Ther 11(11):2526–2534. Scholar
  30. Gorges TM, Kuske A, Rock K, Mauermann O, Muller V, Peine S et al (2016) Accession of tumor heterogeneity by multiplex transcriptome profiling of single circulating tumor cells. Clin Chem 62(11):1504–1515. Scholar
  31. Greulich P, Simons BD (2016) Dynamic heterogeneity as a strategy of stem cell self-renewal. Proc Natl Acad Sci U S A 113(27):7509–7514. Scholar
  32. Hanssen A, Wagner J, Gorges TM, Taenzer A, Uzunoglu FG, Driemel C et al (2016) Characterization of different CTC subpopulations in non-small cell lung cancer. Sci Rep 6:28010. Scholar
  33. Hegemann M, Stenzl A, Bedke J, Chi KN, Black PC, Todenhofer T (2016) Liquid biopsy: ready to guide therapy in advanced prostate cancer? BJU Int 118(6):855–863. Scholar
  34. Howard TD, Paznekas WA, Green ED, Chiang LC, Ma N, Ortiz de Luna RI et al (1997) Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome. Nat Genet 15(1):36–41. Scholar
  35. Hu L, Lau SH, Tzang CH, Wen JM, Wang W, Xie D et al (2004) Association of Vimentin overexpression and hepatocellular carcinoma metastasis. Oncogene 23(1):298–302. Scholar
  36. Hui L, Zhang S, Dong X, Tian D, Cui Z, Qiu X (2013) Prognostic significance of twist and N-cadherin expression in NSCLC. PLoS ONE 8(4):e62171. Scholar
  37. Hyun KA, Koo GB, Han H, Sohn J, Choi W, Kim SI et al (2016) Epithelial-to-mesenchymal transition leads to loss of EpCAM and different physical properties in circulating tumor cells from metastatic breast cancer. Oncotarget 7(17):24677–24687. Scholar
  38. Joosse SA, Gorges TM, Pantel K (2015) Biology, detection, and clinical implications of circulating tumor cells. EMBO Mol Med 7(1):1–11. Scholar
  39. Kallergi G, Papadaki MA, Politaki E, Mavroudis D, Georgoulias V, Agelaki S (2011) Epithelial to mesenchymal transition markers expressed in circulating tumour cells of early and metastatic breast cancer patients. Breast Cancer Res 13(3):R59. Scholar
  40. Karrison TG, Ferguson DJ, Meier P (1999) Dormancy of mammary carcinoma after mastectomy. J Natl Cancer Inst 91(1):80–85CrossRefGoogle Scholar
  41. Khan MA, Tania M, Wei C, Mei Z, Fu S, Cheng J et al (2015) Thymoquinone inhibits cancer metastasis by downregulating TWIST1 expression to reduce epithelial to mesenchymal transition. Oncotarget 6(23):19580–19591. Scholar
  42. Krawczyk N, Meier-Stiegen F, Banys M, Neubauer H, Ruckhaeberle E, Fehm T (2014) Expression of stem cell and epithelial-mesenchymal transition markers in circulating tumor cells of breast cancer patients. Biomed Res Int 2014:415721. Scholar
  43. Kreso A, Dick JE (2014) Evolution of the cancer stem cell model. Cell Stem Cell 14(3):275–291. Scholar
  44. Kulemann B, Liss AS, Warshaw AL, Seifert S, Bronsert P, Glatz T et al (2016) KRAS mutations in pancreatic circulating tumor cells: a pilot study. Tumour Biol 37(6):7547–7554. Scholar
  45. Lamouille S, Xu J, Derynck R (2014) Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol 15(3):178–196. Scholar
  46. Lander AD, Kimble J, Clevers H, Fuchs E, Montarras D, Buckingham M et al (2012) What does the concept of the stem cell niche really mean today? BMC Biol 10:19. Scholar
  47. Larue L, Bellacosa A (2005) Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3’ kinase/AKT pathways. Oncogene 24(50):7443–7454. Scholar
  48. Li X, Marcondes AM, Gooley TA, Deeg HJ (2010) The helix-loop-helix transcription factor TWIST is dysregulated in myelodysplastic syndromes. Blood 116(13):2304–2314. Scholar
  49. Lindsay CR, Le Moulec S, Billiot F, Loriot Y, Ngo-Camus M, Vielh P et al (2016) Vimentin and Ki67 expression in circulating tumour cells derived from castrate-resistant prostate cancer. BMC Cancer 16:168. Scholar
  50. Lu J, Fan T, Zhao Q, Zeng W, Zaslavsky E, Chen JJ et al (2010) Isolation of circulating epithelial and tumor progenitor cells with an invasive phenotype from breast cancer patients. Int J Cancer 126(3):669–683. Scholar
  51. Malara N, Trunzo V, Foresta U, Amodio N, De Vitis S, Roveda L et al (2016) Ex-vivo characterization of circulating colon cancer cells distinguished in stem and differentiated subset provides useful biomarker for personalized metastatic risk assessment. J Transl Med 14(1):133. Scholar
  52. Marie-Egyptienne DT, Lohse I, Hill RP (2013) Cancer stem cells, the epithelial to mesenchymal transition (EMT) and radioresistance: potential role of hypoxia. Cancer Lett 341(1):63–72. Scholar
  53. Marsden CG, Wright MJ, Pochampally R, Rowan BG (2009) Breast tumor-initiating cells isolated from patient core biopsies for study of hormone action. Methods Mol Biol 590:363–375. Scholar
  54. Mathenge EG, Dean CA, Clements D, Vaghar-Kashani A, Photopoulos S, Coyle KM et al (2014) Core needle biopsy of breast cancer tumors increases distant metastases in a mouse model. Neoplasia 16(11):950–960. Scholar
  55. Mego M, Mani SA, Lee BN, Li C, Evans KW, Cohen EN et al (2012) Expression of epithelial-mesenchymal transition-inducing transcription factors in primary breast cancer: the effect of neoadjuvant therapy. Int J Cancer 130(4):808–816. Scholar
  56. Merindol N, Riquet A, Szablewski V, Eliaou JF, Puisieux A, Bonnefoy N (2014) The emerging role of Twist proteins in hematopoietic cells and hematological malignancies. Blood Cancer J 4:e206. Scholar
  57. Mitra A, Mishra L, Li S (2015a) EMT, CTCs and CSCs in tumor relapse and drug-resistance. Oncotarget 6(13):10697–10711. Scholar
  58. Mitra A, Satelli A, Xia X, Cutrera J, Mishra L, Li S (2015b) Cell-surface Vimentin: a mislocalized protein for isolating csVimentin(+) CD133(-) novel stem-like hepatocellular carcinoma cells expressing EMT markers. Int J Cancer 137(2):491–496. Scholar
  59. Mohme M, Riethdorf S, Pantel K (2017) Circulating and disseminated tumour cells—mechanisms of immune surveillance and escape. Nat Rev Clin Oncol 14(3):155–167. Scholar
  60. Nieman MT, Prudoff RS, Johnson KR, Wheelock MJ (1999) N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression. J Cell Biol 147(3):631–644CrossRefGoogle Scholar
  61. Ning Y, Zhang W, Hanna DL, Yang D, Okazaki S, Berger MD et al (2016) Clinical relevance of EMT and stem-like gene expression in circulating tumor cells of metastatic colorectal cancer patients. Pharmacogenomics J. Scholar
  62. O’Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445(7123):106–110. Scholar
  63. Pantel K, Deneve E, Nocca D, Coffy A, Vendrell JP, Maudelonde T et al (2012) Circulating epithelial cells in patients with benign colon diseases. Clin Chem 58(5):936–940. Scholar
  64. Papadaki MA, Kallergi G, Zafeiriou Z, Manouras L, Theodoropoulos PA, Mavroudis D et al (2014) Co-expression of putative stemness and epithelial-to-mesenchymal transition markers on single circulating tumour cells from patients with early and metastatic breast cancer. BMC Cancer 14:651. Scholar
  65. Pardal R, Clarke MF, Morrison SJ (2003) Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 3(12):895–902. Scholar
  66. Park S, Ang RR, Duffy SP, Bazov J, Chi KN, Black PC et al (2014) Morphological differences between circulating tumor cells from prostate cancer patients and cultured prostate cancer cells. PLoS ONE 9(1):e85264. Scholar
  67. Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S et al (2006) Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 25(12):1696–1708. Scholar
  68. Pilati P, Mocellin S, Bertazza L, Galdi F, Briarava M, Mammano E et al (2012) Prognostic value of putative circulating cancer stem cells in patients undergoing hepatic resection for colorectal liver metastasis. Ann Surg Oncol 19(2):402–408. Scholar
  69. Poruk KE, Valero V 3rd, Saunders T, Blackford AL, Griffin JF, Poling J et al (2016) Circulating tumor cell phenotype predicts recurrence and survival in pancreatic adenocarcinoma. Ann Surg 264(6):1073–1081. Scholar
  70. Quintana E, Shackleton M, Foster HR, Fullen DR, Sabel MS, Johnson TM et al (2010) Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized. Cancer Cell 18(5):510–523. Scholar
  71. Rack B, Schindlbeck C, Juckstock J, Andergassen U, Hepp P, Zwingers T et al (2014) Circulating tumor cells predict survival in early average-to-high risk breast cancer patients. J Natl Cancer Inst 106(5).
  72. Riaz M, Sieuwerts AM, Look MP, Timmermans MA, Smid M, Foekens JA et al (2012) High TWIST1 mRNA expression is associated with poor prognosis in lymph node-negative and estrogen receptor-positive human breast cancer and is co-expressed with stromal as well as ECM related genes. Breast Cancer Res 14(5):R123. Scholar
  73. Satelli A, Mitra A, Cutrera JJ, Devarie M, Xia X, Ingram DR et al (2014) Universal marker and detection tool for human sarcoma circulating tumor cells. Cancer Res 74(6):1645–1650. Scholar
  74. Satelli A, Brownlee Z, Mitra A, Meng QH, Li S (2015a) Circulating tumor cell enumeration with a combination of epithelial cell adhesion molecule- and cell-surface vimentin-based methods for monitoring breast cancer therapeutic response. Clin Chem 61(1):259–266. Scholar
  75. Satelli A, Mitra A, Brownlee Z, Xia X, Bellister S, Overman MJ et al (2015b) Epithelial-mesenchymal transitioned circulating tumor cells capture for detecting tumor progression. Clin Cancer Res 21(4):899–906. Scholar
  76. Schilling D, Todenhofer T, Hennenlotter J, Schwentner C, Fehm T, Stenzl A (2012) Isolated, disseminated and circulating tumour cells in prostate cancer. Nat Rev Urol. 9(8):448–463. Scholar
  77. Schneck H, Blassl C, Meier-Stiegen F, Neves RP, Janni W, Fehm T et al (2013) Analysing the mutational status of PIK3CA in circulating tumor cells from metastatic breast cancer patients. Mol Oncol 7(5):976–986. Scholar
  78. Schulze K, Gasch C, Staufer K, Nashan B, Lohse AW, Pantel K et al (2013) Presence of EpCAM-positive circulating tumor cells as biomarker for systemic disease strongly correlates to survival in patients with hepatocellular carcinoma. Int J Cancer 133(9):2165–2171. Scholar
  79. Shipitsin M, Polyak K (2008) The cancer stem cell hypothesis: in search of definitions, markers, and relevance. Lab Invest 88(5):459–463. Scholar
  80. Shmelkov SV, Butler JM, Hooper AT, Hormigo A, Kushner J, Milde T et al (2008) CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors. J Clin Invest 118(6):2111–2120. Scholar
  81. Singh A, Settleman J (2010) EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 29(34):4741–4751. Scholar
  82. Sun YF, Xu Y, Yang XR, Guo W, Zhang X, Qiu SJ et al (2013) Circulating stem cell-like epithelial cell adhesion molecule-positive tumor cells indicate poor prognosis of hepatocellular carcinoma after curative resection. Hepatology 57(4):1458–1468. Scholar
  83. Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2(6):442–454. Scholar
  84. Todenhofer T, Hennenlotter J, Faber F, Wallwiener D, Schilling D, Kuhs U et al (2015) Significance of apoptotic and non-apoptotic disseminated tumor cells in the bone marrow of patients with clinically localized prostate cancer. Prostate 75(6):637–645. Scholar
  85. Todenhofer T, Hennenlotter J, Dorner N, Kuhs U, Aufderklamm S, Rausch S et al (2016) Transcripts of circulating tumor cells detected by a breast cancer-specific platform correlate with clinical stage in bladder cancer patients. J Cancer Res Clin Oncol 142(5):1013–1020. Scholar
  86. Todenhofer T, Azad A, Stewart C, Gao J, Eigl BJ, Gleave ME et al (2017) AR-V7 transcripts in whole blood RNA of patients with metastatic castration resistant prostate cancer correlate with response to abiraterone acetate. J Urol 197(1):135–142. Scholar
  87. Uhr JW, Pantel K (2011) Controversies in clinical cancer dormancy. Proc Natl Acad Sci U S A 108(30):12396–12400. Scholar
  88. Valladares-Ayerbes M, Blanco-Calvo M, Reboredo M, Lorenzo-Patino MJ, Iglesias-Diaz P, Haz M et al (2012) Evaluation of the adenocarcinoma-associated gene AGR2 and the intestinal stem cell marker LGR5 as biomarkers in colorectal cancer. Int J Mol Sci 13(4):4367–4387. Scholar
  89. Van der Auwera I, Peeters D, Benoy IH, Elst HJ, Van Laere SJ, Prove A et al (2010) Circulating tumour cell detection: a direct comparison between the Cell Search System, the AdnaTest and CK-19/mammaglobin RT-PCR in patients with metastatic breast cancer. Br J Cancer 102(2):276–284. Scholar
  90. Vanharanta S, Massague J (2013) Origins of metastatic traits. Cancer Cell 24(4):410–421. Scholar
  91. Vesuna F, van Diest P, Chen JH, Raman V (2008) Twist is a transcriptional repressor of E-cadherin gene expression in breast cancer. Biochem Biophys Res Commun 367(2):235–241. Scholar
  92. Vishnoi M, Peddibhotla S, Yin W, Scamardo AT, George GC, Hong DS et al (2015) The isolation and characterization of CTC subsets related to breast cancer dormancy. Sci Rep 5:17533.
  93. Weissenstein U, Schumann A, Reif M, Link S, Toffol-Schmidt UD, Heusser P (2012) Detection of circulating tumor cells in blood of metastatic breast cancer patients using a combination of cytokeratin and EpCAM antibodies. BMC Cancer 12:206. Scholar
  94. Werner S, Pantel K (2017) Tracing the seeds in the soil. Clin Chem. Scholar
  95. Werner S, Stenzl A, Pantel K, Todenhofer T (2017) Expression of epithelial mesenchymal transition and cancer stem cell markers in circulating tumor cells. Adv Exp Med Biol 994:205–228. Scholar
  96. Wu S, Liu S, Liu Z, Huang J, Pu X, Li J et al (2015) Classification of circulating tumor cells by epithelial-mesenchymal transition markers. PLoS ONE 10(4):e0123976. Scholar
  97. Wushou A, Hou J, Zhao YJ, Shao ZM (2014) Twist-1 up-regulation in carcinoma correlates to poor survival. Int J Mol Sci 15(12):21621–21630. Scholar
  98. Yang MH, Imrali A, Heeschen C (2015) Circulating cancer stem cells: the importance to select. Chin J Cancer Res 27(5):437–449. Scholar
  99. Ye LY, Chen W, Bai XL, Xu XY, Zhang Q, Xia XF et al (2016) Hypoxia-induced epithelial-to-mesenchymal transition in hepatocellular carcinoma induces an immunosuppressive tumor microenvironment to promote metastasis. Cancer Res 76(4):818–830. Scholar
  100. Yi S, Yang ZL, Miao X, Zou Q, Li J, Liang L et al (2014) N-cadherin and P-cadherin are biomarkers for invasion, metastasis, and poor prognosis of gallbladder carcinomas. Pathol Res Pract 210(6):363–368. Scholar
  101. Yoshida GJ, Saya H (2016) Therapeutic strategies targeting cancer stem cells. Cancer Sci 107(1):5–11. Scholar
  102. Yu M, Bardia A, Aceto N, Bersani F, Madden MW, Donaldson MC et al (2014) Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science 345(6193):216–220. Scholar
  103. Zelenko Z, Gallagher EJ, Tobin-Hess A, Belardi V, Rostoker R, Blank J et al (2017) Silencing vimentin expression decreases pulmonary metastases in a pre-diabetic mouse model of mammary tumor progression. Oncogene 36(10):1394–1403. Scholar
  104. Zhang P, Sun Y, Ma L (2015) ZEB1: at the crossroads of epithelial-mesenchymal transition, metastasis and therapy resistance. Cell Cycle 14(4):481–487. Scholar
  105. Zhu QQ, Ma C, Wang Q, Song Y, Lv T (2016) The role of TWIST1 in epithelial-mesenchymal transition and cancers. Tumour Biol 37(1):185–197. Scholar

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Tilman Todenhöfer
    • 1
  • Klaus Pantel
    • 2
    Email author
  • Arnulf Stenzl
    • 1
  • Stefan Werner
    • 2
  1. 1.Department of UrologyEberhard-Karls-UniversityTuebingenGermany
  2. 2.Department of Tumor BiologyUniversity Medical Center Hamburg-EppendorfHamburgGermany

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