Skip to main content

Advertisement

SpringerLink
Log in

The Stem Cell Identity of Testicular Cancer

  • Published:
Stem Cell Reviews Aims and scope Submit manuscript

Abstract

Testicular germ cell tumors account for 1% of all cancers, and are the most common malignancies to affect males between the ages of 15 and 34. Understanding the pathogenesis of testis cancer has been challenging because the molecular and cellular events that result in the formation of germ cell tumors are hypothesized to occur during human fetal development. In this review, the molecular pathways involved in human testis cancer will be presented based on our research in human embryonic stem cells (hESCs), and also research using animal models. Testis germ cell tumors are unique in that the normal germ cell from which the tumor is derived has distinct stem cell characteristics that are shared with pluripotent hESCs. In particular, normal fetal germ cells express the core pluripotent transcription factors NANOG, SOX2 and OCT4. In contrast to hESCs, the germ line is not pluripotent. As a result, germ cell tumorigenesis may arise from loss of germ line-specific inhibitors which in normal germ cells prevent overt pluripotency and self-renewal and when absent in abnormal germ cells, result in the conversion to germ line cancer stem cells. At the conclusion of this review, a model for the molecular events involved in germ cell tumor formation and the relationship between germ cell tumorigenesis and stem cell biology will be presented.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Clark, A. T., Rodriguez, R. T., Bodnar, M. S., Abeyta, M. J., Cedars, M. I., Turek, P. J., et al. (2004). Human STELLAR, NANOG, and GDF3 genes are expressed in pluripotent cells and map to chromosome 12p13, a hotspot for teratocarcinoma. Stem Cells, 22(2), 169–179.

    Article  PubMed  CAS  Google Scholar 

  2. Oosterhuis, J. W., & Looijenga, L. H. (2005). Testicular germ-cell tumours in a broader perspective. Nature Reviews. Cancer, 5(3), 210–222.

    Article  PubMed  CAS  Google Scholar 

  3. Horwich, A., Shipley, J., & Huddart, R. (2006). Testicular germ-cell cancer. Lancet, 367(9512), 754–765.

    Article  PubMed  CAS  Google Scholar 

  4. Skotheim, R. I., Lind, G. E., Monni, O., Nesland, J. M., Abeler, V. M., Fossa, S. D., et al. (2005). Differentiation of human embryonal carcinomas in vitro and in vivo reveals expression profiles relevant to normal development. Cancer Research, 65(13), 5588–5598.

    Article  PubMed  CAS  Google Scholar 

  5. Chambers, I., Colby, D., Robertson, M., Nichols, J., Lee, S., Tweedie, S., et al. (2003). Functional expression cloning of Nanog, a plurippotency sustaining factor in embryonic stem cells. Cell, 113, 643–655.

    Article  PubMed  CAS  Google Scholar 

  6. Mitsui, K., Tokuzawa, Y., Itoh, H., Segawa, K., Murakami, M., Takahashi, K., et al. (2003). The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell, 113, 631–642.

    Article  PubMed  CAS  Google Scholar 

  7. Avilion, A. A., Nicolis, S. K., Pevny, L. H., Perez, L., Vivian, N., & Lovell-Badge, R. (2003). Multipotent cell lineages in early mouse development depend on SOX2 function. Genes & Development, 17, 126–140.

    Article  CAS  Google Scholar 

  8. Kehler, J., Tolkunova, E., Koschorz, B., Pesce, M., Gentile, L., Boiani, M., et al. (2004). OCT4 is required for primordial germ cell survival. EMBO Reports, 5, 1078–1083.

    Article  PubMed  CAS  Google Scholar 

  9. Tam, P. P. L., & Zhou, S. X. (1996). The allocation of epiblast cells to ectoderman and germline lineages is influenced by the position of the cells in the gastrulating mouse embryo. Developments in Biologicals, 178, 124–132.

    CAS  Google Scholar 

  10. Lawson, K. A., & Hage, W. J. (1994). Clonal analysis of the origin of primordial germ cells in the mouse., in Germline Development: Ciba Foundation Symposium (pp. 68–84). West Sussex, UK: Wiley.

    Google Scholar 

  11. Ying, Y. L., Marble, X. M., Lawson, K. A., & Zhao, G. Q. (2000). Requirement of Bmp8b for the generation of primordial germ cells in the mouse. Molecular Endocrinology, 14, 1053–1063.

    Article  PubMed  CAS  Google Scholar 

  12. Ying, Y., & Zhao, Q.-G. (2001). Cooperation of endoderm-derived BMP2 and extraembryonic ectoderm-derived BMP4 in primordial germ cell generation in the mouse. Developments in Biologicals, 232, 484–492.

    CAS  Google Scholar 

  13. Winnier, G., Blessing, M., Labosky, P., & Hogan, B. (1995). Bone morphogenetic protein 4 is required for mesoderm formation and patterning in the mouse. Genes & Development, 9, 2105–2116.

    Article  CAS  Google Scholar 

  14. Ginsburg, M., Snow, M. H. L., & McLaren, A. (1990). Primordial germ cells in the mouse embryo during gastrulation. Development, 110, 521–528.

    PubMed  CAS  Google Scholar 

  15. Okamura, D., Kimura, T., Nakano, T., & Matsui, Y. (2003). Cadherin mediated cell interaction regulates germ cell determination in mice. Development, 130, 6423–6430.

    Article  PubMed  CAS  Google Scholar 

  16. Yabuta, Y., Kurimoto, K., Ohinata, Y., Seki, Y., & Saitou, M. (2006). Gene expression dynamics during germ line specification in mice identified by quantitative single-cell gene expression profiling. Biology of Reproduction, 75, 705–716.

    Article  PubMed  CAS  Google Scholar 

  17. Scholer, H., Dressler, G., Balling, R., Rohdewohld, H., & Gruss, P. (1990). Oct-4: A germ line specific transcription factor mapping to the mouse t-complex. EMBO Journal, 9, 2185–2195.

    PubMed  CAS  Google Scholar 

  18. Yeom, Y. (1996). Germ line regulatory element Oct-4 specific for the totipotent cycle of embryonal cells. Development, 122, 881–894.

    PubMed  CAS  Google Scholar 

  19. Saitou, M., Barton, S. C., & Surani, M. A. (2002). A molecular programme for the specification of germ cell fate in mice. Nature, 418, 293–300.

    Article  PubMed  CAS  Google Scholar 

  20. Yamaguchi, S., Kimura, H., Tada, M., Nakatsuji, N., & Tada, T. (2005). Nanog expression in mouse germ cell development. Gene Expression Patterns, 5, 639–646.

    Article  PubMed  CAS  Google Scholar 

  21. Western, P., Maldonado-Saldivia, J., van den Bergen, J., Hajkova, P., Saitou, M., Barton, S., et al. (2005). Analysis of Esg1 expression in pluripotent cells and the germline reveals similarities with Oct4 and Sox2 and differences between human pluripotent cell lines. Stem Cells, 23(10), 1436–1442.

    Article  PubMed  CAS  Google Scholar 

  22. Sato, M., Kimura, T., Kurokawa, K., Fujita, Y., Abe, K., Masuhara, M., et al. (2002). Identification of PGC7, a new gene expressed specifically in preimplantation embryo’s and germ cells. Mechanisms of Development, 113(1), 91–94.

    Article  PubMed  CAS  Google Scholar 

  23. McKay, D. G., Hertig, A. T., Adams, E. C., & Danziger, S. (1953). Histochemical observation on the germ cells of human embryos. Anatomical Record, 117, 201–219.

    Article  PubMed  CAS  Google Scholar 

  24. Motta, P., Makabe, S., & Nottola, S. (1997). The ultrastructure of human reproduction. I. the natural history of the female germ cell: Origin, migration and differentiation inside the developing ovary. Human Reproduction Update, 3, 281–295.

    Article  PubMed  CAS  Google Scholar 

  25. Gaskell, T. L., Esnal, A., Robinson, L. L., Anderson, R. A., & Saunders, P. T. (2004). Immunohistochemical profiling of germ cells within the human fetal testis: Identification of three subpopulations. Biology of Reproduction, 71, 2012–2021.

    Article  PubMed  CAS  Google Scholar 

  26. Pauls, K., Schorle, H., Jeske, W., Brehm, R., Steger, K., Wernert, N., et al. (2006). Spatial expression of germ cell markers during maturation of human fetal male gonads: an immunohistochemical study. Human Reproduction, 21(2), 397–404.

    Article  PubMed  CAS  Google Scholar 

  27. Ezeh, U. I., Turek, P. J., Reijo, R. A., & Clark, A. T. (2005). Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinoma. Cancer, 104(10), 2255–2265.

    Article  PubMed  CAS  Google Scholar 

  28. Sperger, J. M., Chen, X., Draper, J. S., Antosiewicz, J. E., Chon, C. H., Jones, S. B., et al. (2003). Gene expression patterns in human embryonic stem cells and human pluripotent germ cell tumors. Proceedings of the National Academy of Sciences of the United States of America, 100(23), 13350–13355.

    Article  PubMed  CAS  Google Scholar 

  29. Stevens, L., & Hummel, K. (1957). A description of spontaneous congenital testicular teratomas in strain 129 mice. Journal of the National Cancer Institute, 18, 719–747.

    PubMed  CAS  Google Scholar 

  30. Stevens, L. (1962). The biology of teratomas including evidence indicating their origin from primordial germ cells. Année Biologique, 1, 585–610.

    PubMed  CAS  Google Scholar 

  31. Stevens, L. (1967). Origin of testicular teratomas from primordial germ cells in mice. Journal of the National Cancer Institute, 38, 549–552.

    PubMed  CAS  Google Scholar 

  32. Regenass, U., Freidrich, T., & Stevens, L. (1982). Experimental induction of testicular teratomas in dissociated-reaggregated chimaeric gonads. Journal of Embryology and Experimental Morphology, 72, 153–167.

    Google Scholar 

  33. Noguchi, T., & Stevens, L. (1982). Primordial germ cell proliferation in fetal testes in mouse strains with hig and low incidences of congenital testicular teratomas. Journal of the National Cancer Institute, 69, 907–913.

    Google Scholar 

  34. Noguchi, T., & Noguchi, M. (1985). A recessive mutation (ter) causing germ cell deficiency and a high incidence of congenital testicular teratomas in 129/Sv-ter mice. Journal of the National Cancer Institute, 75, 385–392.

    Google Scholar 

  35. Youngren, K., Coveney, D., Peng, X., Bhattacharya, C., Schmidt, L., Nickerson, M., et al. (2005). The ter mutation in the dead end gene causes germ cell loss and testicular germ cell tumors. Nature, 435, 360–364.

    Google Scholar 

  36. McGlynn, K., Devesa, S., Graubard, B., & Castle, P. (2005). Increasing incidence of testicular germ cell tumors among black men in the United States. Journal of Clinical Oncology, 20, 5757–5761.

    Article  Google Scholar 

  37. Silver, L. (1995). Mouse genetics concepts and applications. 1st ed. New York: Oxford University Press.

    Google Scholar 

  38. Meng, X., de Rooij, D. G., Westerdahl, K., Saarma, M., & Sariola, H. (2001). Promotion of seminomatous tumors by targeted overexpression of glial cell line-derived neurotrophic factor in mouse testis. Cancer Research, 61(8), 3267–3271.

    PubMed  CAS  Google Scholar 

  39. Kanatsu-Shinohara, M., Inoue, K., Lee, J., Yoshimoto, M., Ogonuki, N., Miki, H., et al. (2004). Generation of pluripotent stem cells from neonatal mouse testis. Cell, 119(7), 1001–1012.

    Article  PubMed  CAS  Google Scholar 

  40. Guan, K., Nayernia, K., Maier, L. S., Wagner, S., Dressel, R., Lee, J. H., et al. (2006). Pluripotency of spermatogonial stem cells from adult mouse testis. Nature, 440(7088), 1199–1203.

    Article  PubMed  CAS  Google Scholar 

  41. de Rooij, D. G., & Russell, L. D. (2000). All you wanted to know about spermatogonia but were afraid to ask. Journal of Andrology, 21(6), 776–798.

    PubMed  Google Scholar 

  42. Yoshida, S., Takakura, A., Ohbo, K., Abe, K., Wakabayashi, J., Yamamoto, M., et al. (2004). Neurogenin3 delineates the earliest stages of spermatogenesis in the mouse testis. Developments in Biologicals, 269(2), 447–458.

    CAS  Google Scholar 

  43. Buaas, F. W., Kirsh, A. L., Sharma, M., McLean, D. J., Morris, J. L., Griswold, M. D., et al. (2004). Plzf is required in adult male germ cells for stem cell self-renewal. Nature Genetics, 36(6), 647–652.

    Article  PubMed  CAS  Google Scholar 

  44. Bortvin, A., Eggan, K., Skaletsky, H., Akutsu, H., Berry, D., Yanagimachi, R., et al. (2003). Incomplete reactivation of Oct4-related genes in mouse embryos cloned from somatic nuclei. Development, 130, 1673–1680.

    Article  PubMed  CAS  Google Scholar 

  45. Dettin, L., Ravindranath, N., Hofmann, M. C., & Dym, M. (2003). Morphological characterization of the spermatogonial subtypes in the neonatal mouse testis. Biology of Reproduction, 69(5), 1565–1571.

    Article  PubMed  CAS  Google Scholar 

  46. Schrans-Stassen, B. H., van de Kant, H. J., de Rooij, D. G., & van Pelt, A. M. (1999). Differential expression of c-kit in mouse undifferentiated and differentiating type A spermatogonia. Endocrinology, 140(12), 5894–5900.

    Article  PubMed  CAS  Google Scholar 

  47. Brinster, R. L., & Avarbock, M. R. (1994). Germline transmission of donor haplotype following spermatogonial transplantation [see comments]. Proceedings of the National Academy of Sciences of the United States of America, 91(24), 11303–11307.

    Article  PubMed  CAS  Google Scholar 

  48. Brinster, R. L., & Zimmermann, J. W. (1994). Spermatogenesis following male germ-cell transplantation [see comments]. Proceedings of the National Academy of Sciences of the United States of America, 91(24), 11298–11302.

    Article  PubMed  CAS  Google Scholar 

  49. Kubota, H., Avarbock, M. R., & Brinster, R. L. (2004). Culture conditions and single growth factors affect fate determination of mouse spermatogonial stem cells. Biology of Reproduction, 71(3), 722–731.

    Article  PubMed  CAS  Google Scholar 

  50. Kubota, H., Avarbock, M. R., & Brinster, R. L. (2003). Spermatogonial stem cells share some, but not all, phenotypic and functional characteristics with other stem cells. Proceedings of the National Academy of Sciences of the United States of America, 100(11), 6487–6492.

    Article  PubMed  CAS  Google Scholar 

  51. Kubota, H., Avarbock, M., & Brinster, R. (2004). Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. Proceedings of the National Academy of Sciences of the United States of America, 101, 16489–16494.

    Article  PubMed  CAS  Google Scholar 

  52. Kanatsu-Shinohara, M., Miki, H., Inoue, K., Ogonuki, N., Toyokuni, S., Ogura, A., et al. (2005). Long-term culture of mouse male germline stem cells under serum—or feeder-free conditions. Biology of Reproduction, 72(4), 985–991.

    Article  PubMed  CAS  Google Scholar 

  53. Kanatsu-Shinohara, M., Ogonuki, N., Inoue, K., Miki, H., Ogura, A., Toyokuni, S., et al. (2003). Long-term proliferation in culture and germline transmission of mouse male germline stem cells. Biology of Reproduction, 69(2), 612–616.

    Article  PubMed  CAS  Google Scholar 

  54. Jacobson, G., & Norgaard-Pedersen, B. (1984). Placental alkaline phosphatase in testicular germ cell tumours and in carcinoma in-situ of the testis. an immunohistochemical study. Acta Pathologica, Microbiologica et Immunologica Scandinavica, 92, 323–329.

    Google Scholar 

  55. Almstrup, K., Hoei-Hansen, C. E., Wirkner, U., Blake, J., Schwager, C., Ansorge, W., et al. (2004). Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling. Cancer Reserach, 64(14), 4736–4743.

    Article  PubMed  CAS  Google Scholar 

  56. Hoei-Hansen, C., Alumstrup, K., Nielsen, J., Brask Sonne, S., Graem, N., Skakkebaek, N., et al. (2005). Stem cell pluriptoency factor NANOG is expressed in human fetal gonocytes, testicular carinoma in situ and germ cell tumors. Histopathology, 47, 48–56.

    Article  PubMed  CAS  Google Scholar 

  57. Clark, A. T., Bodnar, M. S., Fox, M., Rodriquez, R., Abeyta, M., Firpo, M., et al. (2004). Spontaneous differentiation of germ cells from human embryonic stem cells in vitro. Human Molecular Genetics, 13, 727–739.

    Article  PubMed  CAS  Google Scholar 

  58. Kee, K., Gonsalves, J., Clark, A., & Ra, R. P. (2006). Bone morphogenetic Proteins induce germ cell differentiation from human embryonic stem cells. Stem Cells and Differentiation, 15, 831–837.

    Article  CAS  Google Scholar 

  59. Toyooka, Y., Tsunekawa, N., Takahashi, Y., Matsui, Y., Satoh, M., & Noce, T. (2000). Expression and intracellular localization of mouse Vasa-homologue protein during germ cell development. Mechanisms of Development, 93, 139–149.

    Article  PubMed  CAS  Google Scholar 

  60. Castrillon, D., Quade, B., Wang, T., Quigley, C., & Crum, C. (2000). The human VASA gene is specifically expressed in the germ cell lineage. Proceedings of the National Academy of Sciences of the United States of America, 97, 9585–9590.

    Article  PubMed  CAS  Google Scholar 

  61. Zeeman, A. M., Stoop, H., Boter, M., Gillis, A. J., Castrillon, D. H. Oosterhuis, J. W., et al. (2002). VASA is a specific marker for both normal and malignant human germ cells. Laboratory Investigation, 82(2), 159–166.

    PubMed  CAS  Google Scholar 

  62. Kaneda, M., Okano, M., Hata, K., Sado, T., Tsujimoto, N., Li, E., et al. (2004) Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature, 429(6994), 900–903.

    Article  PubMed  CAS  Google Scholar 

  63. Kerjean, A., Dupont, J. M., Vasseur, C., Le Tessier, D., Cuisset, L., Paldi, A., et al. (2000). Establishment of the paternal methylation imprint of the human H19 and MEST/PEG1 genes during spermatogenesis. Human Molecular Genetics, 9(14), 2183–2187.

    Article  PubMed  CAS  Google Scholar 

  64. Davis, T. L., Yang, G. J., McCarrey, J. R., & Barolomei, M. S. (2000). The H19 methylation imprint is erased and re-established differentially on the parental alleles during male germ cell development. Human Molecular Genetics, 9, 2885–2894.

    Article  PubMed  CAS  Google Scholar 

  65. Onyango, P., Jiang, S., Uejima, H., Shamblott, M. J., Gearhart, J. D., Cui, H., et al. (2002). Monoallelic expression and methylation of imprinted genes in human and mouse embryonic germ cell lineages. Proceedings of the National Academy of Sciences of the United States of America, 99(16), 10599–10604.

    Article  PubMed  CAS  Google Scholar 

  66. van Gurp, R. J., Oosterhuis, J. W., Kalscheuer, V., Mariman, E. C., & Looijenga, L. H. (1994). Biallelic expression of the H19 and IGF2 genes in human testicular germ cell tumors. Journal of the National Cancer Institute, 86(14), 1070–1075.

    Article  PubMed  Google Scholar 

  67. Mishina, M., Ogawa, O., Kinoshita, H., Oka, H., Okumura, K., Mitsumori, K., et al. (1996). Equivalent parental distribution of frequently lost alleles and biallelic expression of the H19 gene in human testicular germ cell tumors. Japanese Journal of Cancer Research, 87(8), 816–823.

    PubMed  CAS  Google Scholar 

  68. Looijenga, L. H., Rosenberg, C., van Gurp, R. J., Geelen, E., van Echten-Arends, J., de Jong, B., et al. (2000). Comparative genomic hybridization of microdissected samples from different stages in the development of a seminoma and a non-seminoma. Journal of Pathology, 191(2), 187–192.

    Article  PubMed  CAS  Google Scholar 

  69. Looijenga, L., Gillis, A., van Gurp, R., Verkerk, A., & Oosterhuis, J. (1997). X inactivation in human testicular tumors. XIST expression and androgen receptor methylation status. American Journal of Pathology, 151, 581–590.

    PubMed  CAS  Google Scholar 

  70. Hajkova, P., Erhardt, S., Lane, N., Haaf, T., El-Maarri, O., Reik, W., et al. (2002). Epigenetic reprogramming in mouse primordial germ cells. Mechanisms of Development, 117, 15–23.

    Article  PubMed  CAS  Google Scholar 

  71. Trasler, J. M. (2006). Gamete imprinting: Setting epigenetic patterns for the next generation. Reproduction, Fertility and Development, 18(1–2), 63–69.

    Article  Google Scholar 

  72. Seki, Y., Hayashi, K., Itoh, K., Mizugaki, M., Saitou, M., & Matsui, Y. (2005). Extensive and orderly reprogramming of genome-wide chromatin modifications associated with specification and early development of germ cells in mice. Developments in Biologicals, 278, 440–458.

    Article  CAS  Google Scholar 

  73. Ancelin, K., Lange, U., Hajkova, P., Schneider, R., Bannister, A., Kouzarides, T., et al. (2006). Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells. Nature Cell Biology, 8, 623–629.

    Article  PubMed  CAS  Google Scholar 

  74. Holm, T. M., Jackson-Grusby, L., Brambrink, T., Yamada, Y., Rideout, W. M. III, & Jaenisch, R. (2005). Global loss of imprinting leads to widespread tumorigenesis in adult mice. Cancer Cell, 8(4), 275–285.

    Article  PubMed  CAS  Google Scholar 

  75. Gaudet, F., Hodgson, J. G., Eden, A., Jackson-Grusby, L., Dausman, J., Gray, J. W., et al. (2003). Induction of tumors in mice by genomic hypomethylation. Science, 300(5618), 489–492.

    Article  PubMed  CAS  Google Scholar 

  76. Brehm, R., Marks, A., Rey, R., Kliesch, S., Bergmann, M., Steger, K. (2002). Altered expression of connexins 26 and 43 in Sertoli cells in seminiferous tubules infiltrated with carcinoma-in-situ or seminoma. Journal of Pathology, 197(5), 647–653.

    Article  PubMed  CAS  Google Scholar 

  77. Brehm, R., Ruttinger, C., Fischer, P., Gashaw, I., Winterhager, E., Kliesch, S., et al. (2006). Transition from preinvasive carcinoma in situ to seminoma is accompanied by a reduction of connexin 43 expression in Sertoli cells and germ cells. Neoplasia, 8(6), 499–509.

    Article  PubMed  CAS  Google Scholar 

  78. Kliesch, S., Behre, H. M., Hertle, L., & Bergmann, M. (1998). Alteration of Sertoli cell differentiation in the presence of carcinoma in situ in human testes. Journal of Urology, 160(5), 1894–1898.

    Article  PubMed  CAS  Google Scholar 

  79. Donner, J., Kliesch, S., Brehm, R., Bergmann, M. (2004). From carcinoma in situ to testicular germ cell tumour. Apmis, 112(2), 79–88.

    Article  PubMed  Google Scholar 

  80. Davidoff, M. S., Middendorff, R., Koeva, Y., Pusch, W., Jezek, D., & Muller, D. (2001). Glial cell line-derived neurotrophic factor (GDNF) and its receptors GFRalpha-1 and GFRalpha-2 in the human testis. Italian Journal of Anatomy and Embryology, 106(2 Suppl 2), 173–180.

    PubMed  CAS  Google Scholar 

  81. Atkin, N. B., & Baker, M. C. (1983). i(12p): Specific chromosomal marker in seminoma and malignant teratoma of the testis? Cancer Genetics and Cytogenetics, 10(2), 199–204.

    Article  PubMed  CAS  Google Scholar 

  82. Gibas, Z., Prout, G., & Sandberg, A. (1984). Malignant teratoma of the testis with an isochromosome no. 12, i(12p), as the sole structural cytogenetic abnormality. Journal of Urology, 131, 762–763.

    PubMed  CAS  Google Scholar 

  83. Skotheim, R. I., Autio, R., Lind, G. E., Kraggerud, S. M., Andrews, P. W. Monni, O., et al. (2006). Novel genomic aberrations in testicular germ cell tumors by array-CGH, and associated gene expression changes. Cell Oncology, 28(5–6), 315–326.

    CAS  Google Scholar 

  84. Rodriguez, S., Jafer, O., Goker, H., Summersgill, B. M., Zafarana, G., Gillis, A. J., et al. (2003). Expression profile of genes from 12p in testicular germ cell tumors of adolescents and adults associated with i(12p) and amplification at 12p11.2–p12.1. Oncogene, 22(12), 1880–1891.

    Article  PubMed  CAS  Google Scholar 

  85. Sicinski, P., Donaher, J. L., Geng, Y., Parker, S. B., Gardner, H., Park, M. Y., et al. (1996). Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis. Nature, 384(6608), 470–474.

    Article  PubMed  CAS  Google Scholar 

  86. Beumer, T. L., Roepers-Gajadien, H. L., Gademan, I. S., Kal, H. B., & de Rooij, D. G. (2000). Involvement of the D-type cyclins in germ cell proliferation and differentiation in the mouse. Biology of Reproduction, 63(6), 1893–1898.

    Article  PubMed  CAS  Google Scholar 

  87. Bartkova, J., Rajpert-De Meyts, E., Skakkebaek, N. E., Lukas, J., & Bartek, J. (2003). Deregulation of the G1/S-phase control in human testicular germ cell tumours. APMIS, 111(1), 252–265; discussion 265–6.

    Article  PubMed  CAS  Google Scholar 

  88. Schmidt, B. A., Rose, A., Steinhoff, C., Strohmeyer, T., Hartmann, M., & Ackermann, R. (2001). Up-regulation of cyclin-dependent kinase 4/cyclin D2 expression but down-regulation of cyclin-dependent kinase 2/cyclin E in testicular germ cell tumors. Cancer Research, 61(10), 4214–4221.

    PubMed  CAS  Google Scholar 

  89. Kukoski, R., Blonigen, B., Macri, E., Renshaw, A. A., Hoffman, M., Loda, M., et al. (2003). p27 and cyclin E/D2 associations in testicular germ cell tumors: implications for tumorigenesis. Applied Immunohistochemistry & Molecular Morphology, 11(2), 138–143.

    CAS  Google Scholar 

  90. Faussillon, M., Monnier, L., Junien, C., & Jeanpierre, C. (2005). Frequent overexpression of cyclin D2/cyclin-dependent kinase 4 in Wilms’ tumor. Cancer Letter, 221(1), 67–75.

    Article  CAS  Google Scholar 

  91. Becker, K. A., Ghule, P. N., Therrien, J. A., Lian, J. B., Stein, J. L. van Wijnen, A. J., et al. (2006). Self-renewal of human embryonic stem cells is supported by a shortened G1 cell cycle phase. Journal of Cellular Physiology, 209(3), 883–893.

    Article  PubMed  CAS  Google Scholar 

  92. Tres, L. L., & Kierszenbaum, A. L. (2005). The ADAM-integrin-tetraspanin complex in fetal and postnatal testicular cords. Birth Defects Res C Embryo Today, 75(2), 130–141.

    Article  PubMed  CAS  Google Scholar 

  93. Gronborg, M., Kristiansen, T. Z., Iwahori, A., Chang, R., Reddy, R., Sato, N., et al. (2006). Biomarker discovery from pancreatic cancer secretome using a differential proteomic approach. Mol Cell Proteomics, 5(1), 157–171.

    Article  PubMed  CAS  Google Scholar 

  94. Mhawech-Fauceglia, P., Cheney, R. T., & Schwaller, J. (2006). Genetic alterations in urothelial bladder carcinoma: An updated review. Cancer, 106(6), 1205–1216.

    Article  PubMed  CAS  Google Scholar 

  95. Peters, D. G., Kudla, D. M., Deloia, J. A., Chu, T. J., Fairfull, L., Edwards, R. P., et al. (2005). Comparative gene expression analysis of ovarian carcinoma and normal ovarian epithelium by serial analysis of gene expression. Cancer Epidemiology, Biomarkers & Prevention, 14(7), 1717–1723.

    Article  CAS  Google Scholar 

  96. Lian, Q., Yeo, K., Que, J., Tan, E., Yu, F., Yin, Y., et al. (2006). Establishing clonal cell lines with endothelial-like potential from CD9, SSEA-1 cells in embryonic stem cell-derived embryoid bodies. PLoS ONE, 1, e6.

    Article  PubMed  CAS  Google Scholar 

  97. Le Naour, F., Rubinstein, E., Jasmin, C., Prenant, M., & Boucheix, C. (2000). Severely reduced female fertility in CD9-deficient mice. Science, 287(5451), 319–321.

    Article  PubMed  Google Scholar 

  98. Konrad, L., Luers, G. H., Volck-Badouin, E., Keilani, M. M., Laible, L., Aumuller, G., et al. (2006). Analysis of the mRNA expression of the TGF-Beta family in testicular cells and localization of the splice variant TGF-beta2B in testis. Molecular Reproduction and Development, 73(10), 1211–1220.

    Article  PubMed  CAS  Google Scholar 

  99. Chen, C., Ware, S., Sato, A., Houston-Hawkins, D., Habas, R., Matzuk, M., et al. (2005). The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo. Development, 133, 319–329.

    Article  CAS  Google Scholar 

  100. Levine, A., & Brivanlou, A. (2005). GDF3, a BMP inhibitor, regulates cell fate in stem cells and early embryos. Development, 133, 209–216.

    Article  PubMed  CAS  Google Scholar 

  101. Korkola, J., Houldsworth, J., Chadalavada, R. S. V., Olshen, A., Dobrzynski, D., Reuter, V., et al. (2006). Down-regulation of stem cell genes, including those in a 200-kb gene cluster at 12p13.31, is associated with in vivo differentiation of male germ cell tumors. Cancer Research, 66, 820–827.

    Article  PubMed  CAS  Google Scholar 

  102. Konrad, L., Keilani, M. M., Laible, L., Nottelmann, U., & Hofmann, R. (2006). Effects of TGF-betas and a specific antagonist on apoptosis of immature rat male germ cells in vitro. Apoptosis, 11(5), 739–48.

    Article  PubMed  CAS  Google Scholar 

  103. Bouras, M., Tabone, E., Bertholon, J., Sommer, P., Bouvier, R., Droz, J. P., et al. (2000). A novel SMAD4 gene mutation in seminoma germ cell tumors. Cancer Research, 60(4), 922–928.

    PubMed  CAS  Google Scholar 

  104. Levine, A. J., & Brivanlou, A. H. (2006). GDF3 at the crossroads of TGF-beta signaling. Cell Cycle, 5(10), 1069–1073.

    PubMed  CAS  Google Scholar 

  105. Pan, G., & Thomson, J. A. (2007). Nanog and transcriptional networks in embryonic stem cell pluripotency. Cell Research, 17(1), 42–49.

    Article  PubMed  CAS  Google Scholar 

  106. Boyer, L. A., Lee, T. I., Cole, M. F., Johnstone, S. E., Levine, S. S., Zucker, J. P., et al. (2005). Core transcriptional regulatory circuitry in human embryonic stem cells. Cell, 122(6), 947–956.

    Article  PubMed  CAS  Google Scholar 

  107. Yasunami, M., Suzuki, K., & Ohkubo, H. (1996). A novel family of TEA domain-containing transcription factors with distinct spatiotemporal expression patterns. Biochemical and Biophysical Research Communications, 228(2), 365–370.

    Article  PubMed  CAS  Google Scholar 

  108. Payer, B., Saitou, M., Barton, S., Thresher, R., Dixon, J., Zahn, D., et al. (2003). Stella is a maternal effect gene required for normal early development in mice. Current Biology, 13, 2110–2117.

    Article  PubMed  CAS  Google Scholar 

  109. Bortvin, A., Goodheart, M., Liao, M., & Page, D. (2004). Dppa3/Pgc7/stella is a maternal factor and is not required for germ cell specification in mice. BMC Developmental Biology, 4(2).

  110. Nakamura, T., Arai, Y., Umehara, H., Masuhara, M., Kimura, T., Taniguchi, H., et al. (2007). PGC7/Stella protects against DNA demethylation in early embryogenesis. Nature Cell Biology, 9(1), 64–71.

    Article  PubMed  CAS  Google Scholar 

  111. Draper, J., Smith, K., Gokhale, P., Moore, H., Maltby, E., Johnson, J., et al. (2003). Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nature Biotechnology, 1, 53–54.

    Google Scholar 

  112. Herszfeld, D., Wolvetang, E., Langton-Bunker, E., Chung, T. L., Filipczyk, A. A., Houssami, S., et al. (2006). CD30 is a survival factor and a biomarker for transformed human pluripotent stem cells. Nature Biotechnology, 24(3), 351–357.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This research is supported by a training grant from the Lance Armstrong Foundation, and a Career Development Award from the STOP Cancer Foundation to ATC. I gratefully acknowledge Anne Conway for Critical Reading of this Manuscript and Renee Reijo Pera for the work that was initiated in her laboratory at UCSF.

Author information

Authors and Affiliations

  1. Department of Molecular Cell and Developmental Biology, Institute for Stem Cell Biology and Medicine and the Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Box 951606, 621 Charles E Young Drive South, Los Angeles, CA, 90054, USA

    Amander T. Clark

Authors
  1. Amander T. Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amander T. Clark.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Clark, A.T. The Stem Cell Identity of Testicular Cancer. Stem Cell Rev 3, 49–59 (2007). https://doi.org/10.1007/s12015-007-0002-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-007-0002-x

Keywords

Search

Navigation