Cancer Stem Cell Niche and Immune-Active Tumor Microenvironment in Testicular Germ Cell Tumors

  • Katarina Kalavska
  • Lucia Kucerova
  • Silvia Schmidtova
  • Michal Chovanec
  • Michal Mego
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1226)


Testicular germ cell tumors (TGCTs) represent the most common neoplasia among young men. Management of TGCTs is an excellent example of curative outcomes in clinical oncology. The unique sensitivity to cisplatin-based chemotherapy regimens has led to establishing TGCTs as a “model of cancer cure.” However, mechanisms and factors underlying pervasive growth of TGCTs are still poorly understood. It is suggested that unique cancer stem cell (CSC) niche exists in the testicular tumor microenvironment. CSC niche potentially contributes to the progression of germ cell tumors. Furthermore, rich infiltration of TGCTs with immune cells indicates involvement of immune system in biology of this cancer type. This review summarizes current knowledge regarding specific cancer microenvironment in TGCTs and discusses the role of cancer stem cells as well as immune mechanisms in these tumors.


Testicular germ cell tumors Microenvironment Spermatogonial stem cell niche Pluripotency Cancer stem cells Germ cell neoplasia in situ Embryonal carcinoma Hypoxia Immunity Immune privilege Immune cell infiltration Cytokines Gene polymorphism WNT/βcatenin Immune-related biomarkers 


  1. 1.
    Chieffi P (2011) Potential new anticancer molecular targets for the treatment of human testicular seminomas. Mini Rev Med Chem 11(12):1075–1081PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Verdecchia A, Francisci S, Brenner H, Gatta G, Micheli A, Mangone L, Kunkler I, E.-W. Group (2007) Recent cancer survival in Europe: a 2000-02 period analysis of EUROCARE-4 data. Lancet Oncol 8(9):784–796PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Fankhauser CD, Curioni-Fontecedro A, Allmann V, Beyer J, Tischler V, Sulser T, Moch H, Bode PK (2015) Frequent PD-L1 expression in testicular germ cell tumors. Br J Cancer 113(3):411–413PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Znaor A, Lortet-Tieulent J, Jemal A, Bray F (2014) International variations and trends in testicular cancer incidence and mortality. Eur Urol 65(6):1095–1106PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Oosterhuis JW, Looijenga LH (2005) Testicular germ-cell tumours in a broader perspective. Nat Rev Cancer 5(3):210–222PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Rajpert-De Meyts E (2006) Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects. Hum Reprod Update 12(3):303–323PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Diez-Torre A, Silvan U, Diaz-Nunez M, Arechaga J (2010) The role of microenvironment in testicular germ cell tumors. Cancer Biol Ther 10(6):529–536PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Kristensen DM, Sonne SB, Ottesen AM, Perrett RM, Nielsen JE, Almstrup K, Skakkebaek NE, Leffers H, Rajpert-De Meyts E (2008) Origin of pluripotent germ cell tumours: the role of microenvironment during embryonic development. Mol Cell Endocrinol 288(1–2):111–118PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Silvan U, Diez-Torre A, Moreno P, Arluzea J, Andrade R, Silio M, Arechaga J (2013) The spermatogonial stem cell niche in testicular germ cell tumors. Int J Dev Biol 57(2–4):185–195PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Sinha N, Whelan EC, Brinster RL (2019) Isolation, cryopreservation, and transplantation of spermatogonial stem cells. Methods Mol Biol 2005:205–220PubMedCrossRefGoogle Scholar
  11. 11.
    Fon Tacer K, Montoya MC, Oatley MJ, Lord T, Oatley JM, Klein J, Ravichandran R, Tillman H, Kim M, Connelly JP, Pruett-Miller SM, Bookout AL, Binshtock E, Kaminski MM, Potts PR (2019) MAGE cancer-testis antigens protect the mammalian germline under environmental stress. Sci Adv 5(5):eaav4832PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Looijenga LHJ, de Munnik H, Oosterhuis JW (1999) A molecular model for the development of germ cell cancer. Int J Cancer 83(6):809–814PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Rajpert-De Meyts E, McGlynn KA, Okamoto K, Jewett MA, Bokemeyer C (2016) Testicular germ cell tumours. Lancet 387(10029):1762–1774PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Nguyen DX, Bos PD, Massague J (2009) Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer 9(4):274–284PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Plaks V, Kong N, Werb Z (2015) The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells? Cell Stem Cell 16(3):225–238PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Yu Z, Pestell TG, Lisanti MP, Pestell RG (2012) Cancer stem cells. Int J Biochem Cell Biol 44(12):2144–2151PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Almstrup K, Ottesen AM, Sonne SB, Hoei-Hansen CE, Leffers H, Rajpert-De Meyts E, Skakkebaek NE (2005) Genomic and gene expression signature of the pre-invasive testicular carcinoma in situ. Cell Tissue Res 322(1):159–165PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Sperger JM, Chen X, Draper JS, Antosiewicz JE, Chon CH, Jones SB, Brooks JD, Andrews PW, Brown PO, Thomson JA (2003) Gene expression patterns in human embryonic stem cells and human pluripotent germ cell tumors. Proc Natl Acad Sci U S A 100(23):13350–13355PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Pierpont TM, Lyndaker AM, Anderson CM, Jin Q, Moore ES, Roden JL, Braxton A, Bagepalli L, Kataria N, Hu HZ, Garness J, Cook MS, Capel B, Schlafer DH, Southard T, Weiss RS (2017) Chemotherapy-induced depletion of OCT4-positive cancer stem cells in a mouse model of malignant testicular cancer. Cell Rep 21(7):1896–1909PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Hombach-Klonisch S, Paranjothy T, Wiechec E, Pocar P, Mustafa T, Seifert A, Zahl C, Gerlach KL, Biermann K, Steger K, Hoang-Vu C, Schulze-Osthoff K, Los M (2008) Cancer stem cells as targets for cancer therapy: selected cancers as examples. Arch Immunol Ther Exp 56(3):165–180CrossRefGoogle Scholar
  21. 21.
    Rodda DJ, Chew JL, Lim LH, Loh YH, Wang B, Ng HH, Robson P (2005) Transcriptional regulation of nanog by OCT4 and SOX2. J Biol Chem 280(26):24731–24737PubMedCrossRefGoogle Scholar
  22. 22.
    Nettersheim D, Vadder S, Jostes S, Heimsoeth A, Schorle H (2019) TCam-2 cells deficient for SOX2 and FOXA2 are blocked in differentiation and maintain a seminoma-like cell fate in vivo. Cancers (Basel) 11(5):E728CrossRefGoogle Scholar
  23. 23.
    ten Berge D, Kurek D, Blauwkamp T, Koole W, Maas A, Eroglu E, Siu RK, Nusse R (2011) Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells. Nat Cell Biol 13(9):1070–1075PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Ying QL, Wray J, Nichols J, Batlle-Morera L, Doble B, Woodgett J, Cohen P, Smith A (2008) The ground state of embryonic stem cell self-renewal. Nature 453(7194):519–523PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Chovanec M, Cierna Z, Miskovska V, Machalekova K, Kalavska K, Rejlekova K, Svetlovska D, Macak D, Spanik S, Kajo K, Babal P, Mego M, Mardiak J (2018) Betacatenin is a marker of poor clinical characteristics and suppressed immune infiltration in testicular germ cell tumors. BMC Cancer 18(1):1062PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Silvan U, Diez-Torre A, Arluzea J, Andrade R, Silio M, Arechaga J (2009) Hypoxia and pluripotency in embryonic and embryonal carcinoma stem cell biology. Differentiation 78(2–3):159–168PubMedCrossRefGoogle Scholar
  27. 27.
    Silvan U, Arlucea J, Andrade R, Diez-Torre A, Silio M, Konerding MA, Arechaga J (2009) Angiogenesis and vascular network of teratocarcinoma from embryonic stem cell transplant into seminiferous tubules. Br J Cancer 101(1):64–70PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Fujii T, Otsuki T, Moriya T, Sakaguchi H, Kurebayashi J, Yata K, Uno M, Kobayashi T, Kimura T, Jo Y, Kinugawa K, Furukawa Y, Morioka M, Ueki A, Tanaka H (2002) Effect of hypoxia on human seminoma cells. Int J Oncol 20(5):955–962PubMedGoogle Scholar
  29. 29.
    Kalavska K, Cierna Z, Chovanec M, Takacova M, Svetlovska D, Miskovska V, Obertova J, Palacka P, Rajec J, Sycova-Mila Z, Machalekova K, Kajo K, Spanik S, Mardiak J, Babal P, Pastorekova S, Mego M (2017) Prognostic value of intratumoral carbonic anhydrase IX expression in testicular germ cell tumors. Oncol Lett 13(4):2177–2185PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Osinsky S, Zavelevich M, Vaupel P (2009) Tumor hypoxia and malignant progression. Exp Oncol 31(2):80–86PubMedPubMedCentralGoogle Scholar
  31. 31.
    Scheri KC, Leonetti E, Laino L, Gigantino V, Gesualdi L, Grammatico P, Bizzari M, Franco R, Oosterhuis JW, Stoop H, Looijenga LHJ, Ricci G, Catizone A (2018) C-MET receptor as potential biomarker and target molecule for malignant testicular germ cell tumors. Oncotarget 9(61):31842–31860PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Fijak M, Meinhardt A (2006) The testis in immune privilege. Immunol Rev 213:66–81PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Wang M, Fijak M, Hossain H, Markmann M, Nusing RM, Lochnit G, Hartmann MF, Wudy SA, Zhang L, Gu H, Konrad L, Chakraborty T, Meinhardt A, Bhushan S (2017) Characterization of the micro-environment of the testis that shapes the phenotype and function of testicular macrophages. J Immunol 198(11):4327–4340PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Chovanec M, De Giorgi U, Mego M (2018) Immune-related concepts in biology and treatment of germ-cell tumors. Adv Urol 2018:3718165PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Marshall AH, Dayan AD (1964) An immune reaction in man against seminomas, dysgerminomas, pinealomas, and the mediastinal tumours of similar histological appearance? Lancet 2(7369):1102–1104PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Bell DA, Flotte TJ, Bhan AK (1987) Immunohistochemical characterization of seminoma and its inflammatory cell infiltrate. Hum Pathol 18(5):511–520PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Saint F, Leroy X, Graziana JP, Moukassa D, Gosselin B, Biserte J, Chopin D, Rigot JM (2002) Dendritic cell infiltration in a patient with seminomatous germ cell tumor of the testis: is there a relationship with infertility and tumor stage? J Urol 167(4):1643–1647PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Yakirevich E, Lefel O, Sova Y, Stein A, Cohen O, Izhak OB, Resnick MB (2002) Activated status of tumour-infiltrating lymphocytes and apoptosis in testicular seminoma. J Pathol 196(1):67–75PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Bols B, Jensen L, Jensen A, Braendstrup O (2000) Immunopathology of in situ seminoma. Int J Exp Pathol 81(3):211–217PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Hvarness T, Nielsen JE, Almstrup K, Skakkebaek NE, Rajpert-De Meyts E, Claesson MH (2013) Phenotypic characterisation of immune cell infiltrates in testicular germ cell neoplasia. J Reprod Immunol 100(2):135–145PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Klein B, Haggeney T, Fietz D, Indumathy S, Loveland KL, Hedger M, Kliesch S, Weidner W, Bergmann M, Schuppe HC (2016) Specific immune cell and cytokine characteristics of human testicular germ cell neoplasia. Hum Reprod 31(10):2192–2202PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Klein B, Schuppe HC, Bergmann M, Hedger MP, Loveland BE, Loveland KL (2017) An in vitro model demonstrates the potential of neoplastic human germ cells to influence the tumour microenvironment. Andrology 5(4):763–770PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Chovanec M, Mego M, Cholujova D, Gronesova P, Miskovska V, Sycova-Mila Z, Usakova V, Svetlovska D, Bujdak P, Spanik S, Ondrus D, Mardiak J (2015) A cytokine and angiogenic factor (CAF) analysis in plasma in testicular germ cell tumor patients (TGCTs). J Clin Oncol 33(15_suppl):e15552–e15552CrossRefGoogle Scholar
  44. 44.
    Mardiak J, Cholujova D, Jurisica I, Gronesova P, Miskovska V, Obertova J, Palacka P, Rajec J, Sycova-Mila Z, Usakova V, Vertakova-Krakovska B, Chovanec M, Svetlovska D, Salek T, Bujdak P, Spanik S, Ondrus D, Mego M (2013) A cytokine and angiogenic factor (CAF) analysis in plasma in testicular germ cell tumor patients (TGCTs). J Clin Oncol 31(15_Suppl):e15599–e15599Google Scholar
  45. 45.
    Svetlovska D, Miskovska V, Cholujova D, Gronesova P, Cingelova S, Chovanec M, Sycova-Mila Z, Obertova J, Palacka P, Rajec J, Kalavska K, Usakova V, Luha J, Ondrus D, Spanik S, Mardiak J, Mego M (2017) Plasma cytokines correlated with disease characteristics, progression-free survival, and overall survival in testicular germ-cell tumor patients. Clin Genitourin Cancer 15(3):411–416. e412PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Purdue MP, Sakoda LC, Graubard BI, Welch R, Chanock SJ, Sesterhenn IA, Rubertone MV, Erickson RL, McGlynn KA (2007) A case-control investigation of immune function gene polymorphisms and risk of testicular germ cell tumors. Cancer Epidemiol Biomark Prev 16(1):77–83CrossRefGoogle Scholar
  47. 47.
    Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C, Schultz N (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2(5):401–404CrossRefPubMedGoogle Scholar
  48. 48.
    Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, Cerami E, Sander C, Schultz N (2013) Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 6(269):pl1PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Hollern DP, Hoadley K, Vincent B, Perou CM, TCGA Testicular Germ Cell Tumor Analysis Working Group (2017) Abstract 3703: a genomic characterization of testicular germ cell tumor immune microenvironment. Cancer Res 77(13 Supplement):3703–3703Google Scholar
  50. 50.
    Schweyer S, Soruri A, Peters J, Wagner A, Radzun HJ, Fayyazi A (2003) Malignant germ cell tumours of the testis express interferon-gamma, but are resistant to endogenous interferon-gamma. Br J Cancer 89(5):915–921PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Harlin H, Meng Y, Peterson AC, Zha Y, Tretiakova M, Slingluff C, McKee M, Gajewski TF (2009) Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment. Cancer Res 69(7):3077–3085PubMedCrossRefGoogle Scholar
  52. 52.
    Ji RR, Chasalow SD, Wang L, Hamid O, Schmidt H, Cogswell J, Alaparthy S, Berman D, Jure-Kunkel M, Siemers NO, Jackson JR, Shahabi V (2012) An immune-active tumor microenvironment favors clinical response to ipilimumab. Cancer Immunol Immunother 61(7):1019–1031PubMedCrossRefGoogle Scholar
  53. 53.
    Spranger S, Bao R, Gajewski TF (2015) Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity. Nature 523(7559):231–235PubMedCrossRefGoogle Scholar
  54. 54.
    Meng J, Greenlee AR, Taub CJ, Braun RE (2011) Sertoli cell-specific deletion of the androgen receptor compromises testicular immune privilege in mice. Biol Reprod 85(2):254–260PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Kersemaekers AM, van Weeren PC, Oosterhuis JW, Looijenga LH (2002) Involvement of the Fas/FasL pathway in the pathogenesis of germ cell tumours of the adult testis. J Pathol 196(4):423–429PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Schmelz HU, Abend M, Kraft K, Hauck EW, Weidner W, Van Beuningen D, Sparwasser C (2002) Fas/Fas ligand system and apoptosis induction in testicular carcinoma. Cancer 95(1):73–81PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Okazaki T, Honjo T (2007) PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol 19(7):813–824PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Francisco LM, Sage PT, Sharpe AH (2010) The PD-1 pathway in tolerance and autoimmunity. Immunol Rev 236:219–242PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Kyi C, Postow MA (2014) Checkpoint blocking antibodies in cancer immunotherapy. FEBS Lett 588(2):368–376PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Noh H, Hu J, Wang X, Xia X, Satelli A, Li S (2015) Immune checkpoint regulator PD-L1 expression on tumor cells by contacting CD11b positive bone marrow derived stromal cells. Cell Commun Signal 13:14PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Cierna Z, Mego M, Miskovska V, Machalekova K, Chovanec M, Svetlovska D, Hainova K, Rejlekova K, Macak D, Spanik S, Ondrus D, Kajo K, Mardiak J, Babal P (2016) Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors. Ann Oncol 27(2):300–305PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Chovanec M, Cierna Z, Miskovska V, Machalekova K, Kalavska K, Rejlekova K, Svetlovska D, Macak D, Spanik S, Kajo K, Babal P, Mardiak J, Mego M (2017) Systemic immune-inflammation index is prognostic in testicular germ cell tumors with PD-L1 expressing tumor infiltrating lymphocytes. J Clin Oncol 35(15_suppl):e16042CrossRefGoogle Scholar
  63. 63.
    Siska PJ, Johnpulle RAN, Zhou A, Bordeaux J, Kim JY, Dabbas B, Dakappagari N, Rathmell JC, Rathmell WK, Morgans AK, Balko JM, Johnson DB (2017) Deep exploration of the immune infiltrate and outcome prediction in testicular cancer by quantitative multiplexed immunohistochemistry and gene expression profiling. Oncoimmunology 6(4):e1305535PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Yamada Y, Nakagawa T, Sugihara T, Horiuchi T, Yoshizaki U, Fujimura T, Fukuhara H, Urano T, Takayama K, Inoue S, Kume H, Homma Y (2016) Prognostic value of CD66b positive tumor-infiltrating neutrophils in testicular germ cell tumor. BMC Cancer 16(1):898PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Adra N, Einhorn LH, Althouse SK, Ammakkanavar NR, Musapatika D, Albany C, Vaughn D, Hanna NH (2018) Phase II trial of pembrolizumab in patients with platinum refractory germ-cell tumors: a Hoosier Cancer research network study GU14-206. Ann Oncol 29(1):209–214PubMedCrossRefGoogle Scholar
  66. 66.
    Zschabitz S, Lasitschka F, Hadaschik B, Hofheinz RD, Jentsch-Ullrich K, Gruner M, Jager D, Grullich C (2017) Response to anti-programmed cell death protein-1 antibodies in men treated for platinum refractory germ cell cancer relapsed after high-dose chemotherapy and stem cell transplantation. Eur J Cancer 76:1–7PubMedCrossRefGoogle Scholar
  67. 67.
    Zschabitz S, Lasitschka F, Jager D, Grullich C (2016) Activity of immune checkpoint inhibition in platinum refractory germ-cell tumors. Ann Oncol 27(7):1356–1360PubMedCrossRefGoogle Scholar
  68. 68.
    Chi EA, Schweizer MT (2017) Durable response to immune checkpoint blockade in a platinum-refractory patient with nonseminomatous germ cell tumor. Clin Genitourin Cancer 15(5):e855–e857PubMedCrossRefGoogle Scholar
  69. 69.
    Mego M, Svetlovska D, Chovanec M, Reckova M, Rejlekova K, Obertova J, Palacka P, Sycova-Mila Z, De Giorgi U, Mardiak J (2019) Phase II study of avelumab in multiple relapsed/refractory germ cell cancer. Investig New Drugs 37:748–754CrossRefGoogle Scholar
  70. 70.
    Albany C, Hever-Jardine MP, von Herrmann KM, Yim CY, Tam J, Warzecha JM, Shin L, Bock SE, Curran BS, Chaudhry AS, Kim F, Sandusky GE, Taverna P, Freemantle SJ, Christensen BC, Einhorn LH, Spinella MJ (2017) Refractory testicular germ cell tumors are highly sensitive to the second generation DNA methylation inhibitor guadecitabine. Oncotarget 8(2):2949–2959PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Dorssers LCJ, Gillis AMJ, Stoop H, van Marion R, Nieboer MM, van Riet J, van de Werken HJG, Oosterhuis JW, de Ridder J, Looijenga LHJ (2019). Molecular heterogeneity and early metastatic clone selection in testicular germ cell cancer development. Br J Cancer 120(4):444–452.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Schmidtova S, Kalavska K, Mego M, Gercakova K, Kucerova L (2018). Inhibition of aldehyde dehydrogenase by disulfiram and poly (ADPribose) polymerase by veliparib reverts cisplatin resistance in embryonal carcinoma cell line. In 9th Copenhagen workshop on testicular germ cell cancer. P. 70.Google Scholar
  73. 73.
    Bonatelli M, Silva ECA, Cárcano FM, Zaia MG, Lopes LF, Scapulatempo-Neto C, Pinheiro C (2019). The Warburg effect is associated with tumor aggressiveness in testicular germ cell tumors. Front Endocrinol 10: 417.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Katarina Kalavska
    • 1
    • 2
  • Lucia Kucerova
    • 2
  • Silvia Schmidtova
    • 2
  • Michal Chovanec
    • 3
  • Michal Mego
    • 1
    • 2
    • 3
  1. 1.Translational Research Unit, Faculty of MedicineComenius University and National Cancer InstituteBratislavaSlovakia
  2. 2.Department of Molecular OncologyCancer Research Institute, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of SciencesBratislavaSlovakia
  3. 3.Faculty of Medicine, 2nd Department of OncologyComenius University and National Cancer InstituteBratislavaSlovakia

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