Differentiation in Teratocarcinoma: Its Implications in Therapy

  • Perinchery Narayan
  • William C. Dewolf
  • Wendell C. Speers
Part of the Cancer Treatment and Research book series (CTAR, volume 19)


Testes cancer is the most common solid tumor affecting males 20–34 years of age. Recent epidemiologic evidence suggests a growing incidence in the United States and Europe. For example, in the USA from 1935–39, testicular cancer represented 13% of all cancers in the 15–34 age group; whereas in 1975–76, the proportional incidence increased significantly to 19% [1]. In addition to its increasing prominence in clinical oncology, testes cancer has demonstrated several unique features that has attracted the attention of researchers from several fields. Specifically, the teratocarcinoma model has assumed an important role in fundamental research involving not only mechanisms of malignant transformation but also development of the embryo and fetus. This perhaps is not unexpected because teratocarcinoma is a tumor of germ-line origin with the capacity to produce differentiated cell types representing derivatives of the primary germ layers and, therefore, potentially represents a direct link between malignancy and development.


Germ Cell Embryoid Body Embryonal Carcinoma Testis Cancer Teratocarcinoma Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Schottenfeld D, Warshauer M, Sherlock S, Zauber A, Leder M, Payne R: The epidemiology of testicular cancer in young adults. Am J Epidemiol 112:232–246, 1980.PubMedGoogle Scholar
  2. 2.
    Martin G: Teratocarcinoma and mammalian embryogenesis. Science 209:768–776, 1980.PubMedCrossRefGoogle Scholar
  3. 3.
    Stevens LC: Genetic influences on teratocarcinogenesis and parthenogenesis. In: Mammalian Genetics and Cancer, Russell ES (ed). New York: Alan R Liss, pp 93–104, 1981.Google Scholar
  4. 4.
    Stevens LC, Hummel KP: A description of spontaneous congenital testicular teratoma in strain 129 mice. J Natl Cancer Inst 18:719–747, 1957.PubMedGoogle Scholar
  5. 5.
    Stevens LC, Little CC: Spontaneous testicular teratomas in an inbred strain of mice. Proc Natl Acad Sci USA 40:1080–1087, 1954.PubMedCrossRefGoogle Scholar
  6. 6.
    Caroll P, De Wolf WC: Immune properties of human teratocarcinoma I. Human teratocarcinoma targets distinguish between natural killer and activated killer cells. J Immunol 131:1007–1010, 1983.Google Scholar
  7. 7.
    Carroll P, De Wolf WC: Immune properties on human teratocarcinoma II. Sensivity to AK mediated cytolysis is differentiation dependent (submitted).Google Scholar
  8. 8.
    Damjanov I, Fox N, Knowles BB, Solter D, Lange P, Fraley EE: Immunohistochemical localisation of murine stage specific antigens in human testicular germ cell tumors. Am J Pathol 108:225–230, 1982.PubMedGoogle Scholar
  9. 9.
    Ducibella T, Anderson D, Aalberg J, De Wolf WC: Cell surface polarization, tight junctions and eccentric inner cells characterize human teratocarcinoma embryoid bodies. Dev Biol 94:197–205, 1982.PubMedCrossRefGoogle Scholar
  10. 10.
    Cohnheim JF: Lectures on General Pathology. London, 1889.Google Scholar
  11. 11.
    Mintz B, Fleischman RA: Teratocarcinomas and other neoplasms as developmental defects in gene expression. Adv Cancer Res 34:211–278, 1981.PubMedCrossRefGoogle Scholar
  12. 12.
    Pierce GB, Cox WF Jr: In: Cell differentiation and neoplasia, Saunders GF (ed). New York: Raven Press, pp 57–66, 1978.Google Scholar
  13. 13.
    Pollack R, Risser R, Conlon S, Rifkin D: Plasminogen activator production accompanies loss of anchorage regulation in transformation of primary rat embryo cells by simian virus 40. Proc Natl Acad Sci USA 17:4792–4796, 1974.CrossRefGoogle Scholar
  14. 14.
    Sherman MI, Strickland S, Reich E: Differentiation of mouse embryonic and teratocarcinoma cells in vitro: plasminogen activator production. Cancer Res 36:4208–4216, 1976.PubMedGoogle Scholar
  15. 15.
    Coggin JH, Anderson NG: Cancer differentiation and embryonic antigens: some central problems. Adv Cancer Res 19:105–165, 1974.PubMedCrossRefGoogle Scholar
  16. 16.
    Burger M, Noonan KD: Restoration of normal growth by covering of agglutinin sites on tumor cell surface. Nature 228:512–515, 1970.PubMedCrossRefGoogle Scholar
  17. 17.
    Mascona AA: Embryonic and neoplastic cell surfaces. Availability of receptors for concanavalin A and wheat germ agglutinin. Science 171:905–907, 1971.CrossRefGoogle Scholar
  18. 18.
    Folkman J: Antiangiogenesis: New concept for therapy of solid tumors. Ann Surg 175:409–446, 1972.PubMedCrossRefGoogle Scholar
  19. 19.
    Tuffery M, Bishun NP, Barnes RD: Porosity of the mouse placenta to maternal cells. Nature 221:1029–1030, 1969.CrossRefGoogle Scholar
  20. 20.
    Sinkovics JG, DiSiaia PJ, Rutledge FN: Tumor immunology and evolution of the placenta. Lancet 2:1190–1191, 1970.PubMedCrossRefGoogle Scholar
  21. 21.
    Stein G, Stein J, Thompson J: Chromosomal proteins in transformed and neoplastic cells. Cancer Res 38:1181–1201, 1978.PubMedGoogle Scholar
  22. 22.
    Mintz B, Illmensee K: Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc Natl Acad Sci USA 72:3585–3589, 1975.PubMedCrossRefGoogle Scholar
  23. 23.
    Brintser RL: The effect of cells transferred into mouse blastocyst on subsequent development. J Exp Med 140:1049–1056, 1974.CrossRefGoogle Scholar
  24. 24.
    Papaioannou VE, McBurney MW, Gardner RL, Evans MJ: Fate of teratocarcinoma cells injected into early mouse embryos. Nature 250:70–73, 1975.CrossRefGoogle Scholar
  25. 25.
    Martin G: Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 78:7634–7638, 1981.PubMedCrossRefGoogle Scholar
  26. 26.
    Evans MJ, Kaufman MH: Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154, 1981.PubMedCrossRefGoogle Scholar
  27. 27.
    Stevens LC: Embryology of testicular teratomas in strain 129 mice. J Natl Cancer Inst 23:1249–1261, 1959.PubMedGoogle Scholar
  28. 28.
    Dixon FJ, Moore RA: In: Atlas of Tumor Pathology, Section 8, Fasc 32b and 32. Washington, DC: Armed Forces Institute of Pathology, 1952.Google Scholar
  29. 29.
    Artzt K, Dubois P, Bennett D, Condamine H, Babinet C, Jacob F: Surface antigens common to mouse cleavage embryos and primitive teratocarcinoma cells in culture. Proc Natl Acad Sci USA 70:2988–2992, 1973.PubMedCrossRefGoogle Scholar
  30. 30.
    Gachelin G, Fellous M, Guenet JL, Jacob F: Developmental expression of an early embryonic antigen common to mouse spermatozoa and cleavage embryos and to human spermatozoa: its expression during spermatogenesis. Dev Biol 50:310–320, 1976.PubMedCrossRefGoogle Scholar
  31. 31.
    Jacob F: Mouse teratocarcinoma and embryonic antigens. Immunol Rev 33:3–32, 1977.PubMedCrossRefGoogle Scholar
  32. 32.
    Hogan B, Fellous M, Avner P, Jacob F: Isolation of a human teratoma cell line which expresses F9 antigen. Nature 270:515–518, 1977.PubMedCrossRefGoogle Scholar
  33. 33.
    Holden S, Bernard O, Artzt K, Whitmore W Jr, Bennett D: Human and mouse embryonal carcinoma cells in culture share an embryonic antigen (F9). Nature 270:518–520, 1977.PubMedCrossRefGoogle Scholar
  34. 34.
    Solter D, Knowles BB: Monoclonal antibody defining a stage specific mouse embryonic antigen (SSEA-1). Proc Natl Acad Sci USA 75:5565–5569, 1978.PubMedCrossRefGoogle Scholar
  35. 35.
    Shevinsky LH, Knowles BB, Damjanov I, Solter D: Monoclonal antibody to murine embryos defines a stage specific embryonic antigen expressed on mouse embryos and human teratocarcinoma cells. Cell 30:667–670, 1982.CrossRefGoogle Scholar
  36. 36.
    Hamilton M, Anderson DJ: Antibodies to antigens on teratocarcinoma cells are associated with parity in mice. Biol Reproduction 27:104–109, 1982.CrossRefGoogle Scholar
  37. 37.
    Moon RC: Relationship between previous reproductive history and chemically induced mammary cancer in rats. Int J Cancer 4:312–317, 1969.PubMedCrossRefGoogle Scholar
  38. 38.
    Castro JE, Hunt R, Lace EM, Medawar P: Implications of the fetal antigens theory for fetal transplantation. Cancer Res 34:2055–2060, 1974.PubMedGoogle Scholar
  39. 39.
    Hamilton MS, Beer AE, May RD, Vitetta ES: The influence of immunization of female mice with F9 teratocarcinoma cells on their reproductive performance. Transpl Proc 11(1):1067–1072, 1979.Google Scholar
  40. 40.
    Baldwin RW, Vose BM: The expression of a phase specific fetal antigen on rat embryo cells. Transplant 18(6):525–530, 1974.CrossRefGoogle Scholar
  41. 41.
    Bansal SR, Mark R, Rhoads JE, Bansal SC: Effect of embryonic tissue immunization on chemically induced gastrointestinal tumors in rats I: Can embryonic antigens act as rejection antigens? J Natl Cancer Inst 61:189–201, 1978.PubMedGoogle Scholar
  42. 42.
    Vojtiskova M, Pokorna Z, Draber P: Autoimmune damage to spermatogenesis in rodents immunized with mouse F9 embryonic carcinoma cells. Proc Natl Acad Sci USA 80:459–461, 1983.PubMedCrossRefGoogle Scholar
  43. 43.
    Haywood GR, McKhaun CF: Antigenic specificities on murine sarcoma cells. Reciprocal relationship between normal transplantation antigens (H-2) and tumor specific immunogenicity. J Exp Med 133:1171–1187, 1971.PubMedCrossRefGoogle Scholar
  44. 44.
    Cikes M, Friberg S, Klein G: Progressive loss of H-2 antigens with concomitant increase of cell surface antigen(s) determined by Moloney leukemia virus in cultured murine lymphomas. J Natl Cancer Inst 50:347–362, 1973.PubMedGoogle Scholar
  45. 45.
    Tsakraklides E, Smith C, Kersey JH, Good RA: Transplantation antigens (H-2) or virally and chemically transformed Balb/3T3 fibroblasts in culture. J Natl Cancer Inst 52:1499–1504, 1974.PubMedGoogle Scholar
  46. 46.
    Callahan GH, Allison JP, Pellegrino MA, Reisfeld RA: Physical association of histocompatibility antigens at tumor cell surfaces. J Immunol 122:70–74, 1979.PubMedGoogle Scholar
  47. 47.
    Schrader JW, Cunningham BA, Edelman GM: Functional interaction of viral and histocompatibility antigens at tumor cell surfaces. Proc Natl Acad Sci USA 72:5066–5070, 1975.PubMedCrossRefGoogle Scholar
  48. 48.
    Flaherty L, Rinchik E: No evidence for foreign H-2 specificities on the EL4 mouse lymphoma. Nature 273:52–53, 1978.PubMedCrossRefGoogle Scholar
  49. 49.
    Fox RI, Weissman IL: Maloney virus induced cells surface antigens and histocompatibility antigens are located on distinct molecules. J Immunol 122:1697–1704, 1979.PubMedGoogle Scholar
  50. 50.
    Invernizzi G, Parmiani G: Tumor associated transplantation antigens of chemically induced sarcomata cross reacting with allogeneic histocompatibility antigens. Nature 254:713–714, 1975.PubMedCrossRefGoogle Scholar
  51. 51.
    Martin JW, Gipson TG, Rice JM: H-2a associated alloantigen expressed by several transplacental induced lung tumors of C3H mice. Nature 265:738–739, 1977.PubMedCrossRefGoogle Scholar
  52. 52.
    Parmiani G, Lembo R: In: Embryonic and Fetal Antigens, Anderson NG, Loggin JH, Cole E (eds). Springfield VA: National Technical Information Service, p 159, 1972.Google Scholar
  53. 53.
    Artzt K, McGormick P, Bennett D: Gene mapping within the T/t complex of the mouse I. t lethal genes are non-allelic. Cell 28:463–470, 1982.PubMedCrossRefGoogle Scholar
  54. 54.
    Artzt K, Shin HS, Bennett D: Gene mapping within the T/t complex of the mouse II. Anomalous position of H-2 complex in t haplotypes. Cell 28:471–476, 1982.PubMedCrossRefGoogle Scholar
  55. 55.
    Silver L, Artzt K, Bennett D: A major testicular celle protein specified by a T/t complex gene. Cell 17:275–284, 1979.PubMedCrossRefGoogle Scholar
  56. 56.
    Shedlovsky A, Clipson L, Vandeberg J, Dove WF: Strong teratocarcinoma transplantation loci Gt-1 and Gt-2, flank H-2. Immunogenetics 7:103, 1978.PubMedCrossRefGoogle Scholar
  57. 57.
    De Wolf WC, Lange PH, Emarson M, Yunis EJ: HLA and testicular cancer. Nature 277:216–217, 1979.CrossRefGoogle Scholar
  58. 58.
    Fraley EE, Lange PH, Kennedy BJ: Germ cell testicular cancer in adults. New Engl J Med 301:1420–1426, 1979.PubMedCrossRefGoogle Scholar
  59. 59.
    Donohue JP, Einhorn LH, Williams SD: Cytoreductive surgery for metastatic testes cancer. Consideration of timing and extent. J Urol 123:876–880, 1980.PubMedGoogle Scholar
  60. 60.
    Mostofi FK, Price EB Jr: In: Tumors of the Male Genital System, Mostofi FK, Price EB Jr (eds). Washington, DC: Armed Forces Institute of Pathology, Fasc, 8, pp 68–71, 1973.Google Scholar
  61. 61.
    Lange PH, Nochomovitz LE, Rosai J, Fraley EE, Kennedy BJ, Bosl G, Brisbane J, Catalona WH, Cochran JS, Comisarow RH, Cummings KB, DeKernion JB, Einhorn LH, Hakala TR, Jewett M, Moore MR, Scardino PT, Streitz JM: Serum alpha fetoprotein and human chorionic gonadotropins in patients with seminoma. J Urol 124(4):472–478, 1980.PubMedGoogle Scholar
  62. 62.
    Kurman RJ, Scardino PT, McIntire KR, Waldman TA, Javadpour N: Cellular localizations of alpha fetoproteins and human chorionic gonadotropins in germ cell tumors using an indirect immunoperoxidase technique. A new approach to classification using tumor markers. Cancer 40:2136–2151, 1977.PubMedCrossRefGoogle Scholar
  63. 63.
    Braunstein GD, Vaitukaitis JL, Carbone PP, Ross GT: Ectopic production of chorionic gonadotropins by neoplasms. Ann Intern Med 78:39–45, 1973.PubMedGoogle Scholar
  64. 64.
    Mostofi FK, Price EB Jr: In: Tumors of the Male Genital System, Mostof FK, Price EB Jr (eds). Washington, DC: Armed Forces Institute of Pathology, Fasc 8, p 74, 1973.Google Scholar
  65. 65.
    Smithers DW: Maturation in human tumors. Lancet 2:949–952, 1969.PubMedCrossRefGoogle Scholar
  66. 66.
    Snyder RN: Completely mature pulmonary metastases from testicular teratocarcinoma: Case report and review of the literature. Cancer 24:810–819, 1969.CrossRefGoogle Scholar
  67. 67.
    Willis GW, Hajdu ST: Histologically benign teratoid metastases of testicular embryonal carcinoma. Am J Clin Pathol 59:338–343, 1973.PubMedGoogle Scholar
  68. 68.
    Merrin C, Baumgartner G, Wajsman Z: Benign transformation of testicular carcinoma by chemotherapy. Lancet 1:43–44, 1975.PubMedCrossRefGoogle Scholar
  69. 69.
    Hong WK, Wittes RE, Hadju ST, Cvitkovic E, Whitmore WF, Golbey RB: The evolution of mature teratoma from malignant testicular tumors. Cancer 40:2987–2992, 1977.PubMedCrossRefGoogle Scholar
  70. 70.
    Oosterhuis WJ, Suurmeyer AJ, Sleyfer DT, Koops HS, Oldhoff J, Fleuren G: Effects of multiple drug chemotherapy on the maturation of retroperitoneal metastases of non-semi nomatous germ cell tumors of the testes. Cancer 51:408–416, 1983.PubMedCrossRefGoogle Scholar
  71. 71.
    Bracken RB, Johnson DE, Frazier OH, Logothetis CJ, Trindade A, Samuels ML: Role of surgery following chemotherapy in stage III germ cell neoplasms. J Urol 129(1):39–43, 1983.PubMedGoogle Scholar
  72. 72.
    Einhorn LH, Donohue J: Cis-diamminedichloroplatinum, vinblastine and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med 87:293–298, 1977.PubMedGoogle Scholar
  73. 73.
    Vugrin D, Cvitkovic E, Whitmore WF, Cheng E, Golbey RB: VAB4 combination chemotherapy in the treatment of metastatic testes tumors. Cancer 47:833–839, 1981.PubMedCrossRefGoogle Scholar
  74. 74.
    Carr BI, Gilchrist KW, Carbone PP: Variable transformation in metastases from testicular germ cell tumors: Need for selective biopsy. J Urol 126 (1):52–54, 1981.PubMedGoogle Scholar
  75. 75.
    Abelev GI: Alpha-fetoprotein as a marker of embryo specific differentiation in normal and tumor tissue. Transplant Rev 20:3–37, 1974.PubMedGoogle Scholar
  76. 76.
    Abelev GI, Assecritova NA, Kraevesky NA: Embryonal serum alpha globulin in cancer patients: diagnostic value. Int J Cancer 2:551–558, 1967.PubMedCrossRefGoogle Scholar
  77. 77.
    Lange PH, Fraley EE: Serum alpha-fetoprotein and human chorionic gonadotropin in the treatment of patients with testicular tumors. Urol Clin North Am 4:393–406, 1977.PubMedGoogle Scholar
  78. 78.
    Scardino PT, Cox HD, Waldman TA, Mclntire RK, Mittemeyer B, Javadpour N: Value of serum markers in the staging and prognosis of germ cell tumors of the testes. J Urol 118:994–999, 1977.PubMedGoogle Scholar
  79. 79.
    Rosen SW, Javadpour N, Calvert I, Kaminska J: Pregnancy specific beta 1, glycoprotein (SP-1) is increased in certain non-seminomatous germ cell tumors. J Natl Cancer Inst 62:1439–1441, 1979.PubMedGoogle Scholar
  80. 80.
    Donohue JP, Einhorn LD, Williams SD: Is adjuvant chemotherapy following retroperitoneal node dissection for non-seminomatous cancer necessary? Urol Clin North Am 7:747–756, 1980.PubMedGoogle Scholar
  81. 81.
    Lange PH, Millan JL, Stigbrandt T, Vessella RL, Ruoslahti E, Fishman WH: Placental alkaline phosphatase as a tumor marker for seminoma. Cancer Res 42:3244–3247, 1982.PubMedGoogle Scholar
  82. 82.
    Ballou B, Levine G, Hakala T, Solter D: Tumor location detected with radioactively labelled monoclonal antibody and external scintigraphy. Science 206:846–847, 1979.CrossRefGoogle Scholar
  83. 83.
    Goldenberg DM, Kim EE, vanNagell JR Jr, Javadpour N: Radioimmunodetection of cancer using radioactive antibodies to human chorionic gonadotropin. Science 208:1284–1286, 1980.PubMedCrossRefGoogle Scholar
  84. 84.
    Narayan P, Scott BK, Millette CF, DeWolf WC: Human spermatogenic cell marker proteins detected by two-dimensional electrophoresis. Gamete Res 7:227–239, 193.Google Scholar
  85. 85.
    Stevens VC: The current status of antipregnancy vaccines based on synthetic factions of HCG. In: Immunological Aspects of Reproduction and Fertility Control, Hearn JP (ed). Baltimore: University Park Press, p 203, 1980.Google Scholar
  86. 86.
    Talwar GP, Das C, Tanden A, Sharma MG, Salahuddin M, Dubey SK: Immunization against hCG: Efficacy and teratological studies in baboons. In: Non-human Private Models for Study of Human Reproduction, Anand Kumar TC (ed). Basel: Karger, p 190, 1980.Google Scholar
  87. 87.
    Goldberg E, Wheat TE, Powell JE, Stevens VC: Reduction of fertility in female baboons immunized with lactate dehydrogenase C4. Fertil Steril 35:214–217, 1981.PubMedGoogle Scholar


  1. 1.
    Kleinsmith LJ, Pierce GB Jr: Multipotentiality of single embryonal carcinoma cells. Cancer Res 24:1544–1552, 1964.PubMedGoogle Scholar
  2. 2.
    Martin GR, Wiley LM, Damjanov I: The development of cystic embryoid bodies in vitro from clonal teratocarcinoma stem cells. Dev Biol 61:230–244, 1977.PubMedCrossRefGoogle Scholar
  3. 3.
    Pierce GB, Dixon FJ, Verney EL: Teratocarcinogenic and tissue-forming potentialities of cell types comprising neoplastic embryoid bodies. Lab Invest 9:583–602, 1960.PubMedGoogle Scholar
  4. 4.
    Strickland S, Mahdavi V: The induction of differentiation in teratocarcinoma stem cells by retinoic acid. Cell 15:393–403, 1978.PubMedCrossRefGoogle Scholar
  5. 5.
    Strickland S, Sawey MJ: Studies on the effect of retinoids on the differentiation of teratocarcinoma stem cells in vitro and in vivo. Dev Biol 78:76–85, 1980.PubMedCrossRefGoogle Scholar
  6. 6.
    Speers WC: Conversion of malignant murine embryonal carcinomas to benign teratomas by chemical induction of differentiation in vivo. Cancer Res 42:1843–1849, 1982.PubMedGoogle Scholar

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© Martinus Nijhoff Publishers, Boston 1984

Authors and Affiliations

  • Perinchery Narayan
  • William C. Dewolf
  • Wendell C. Speers

There are no affiliations available

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