The Human Melanocyte System as a Model for Studies on Tumor Progression

  • Istvan Valyi-Nagy
  • Ulrich Rodeck
  • Roland Kath
  • Maria Laura Mancianti
  • Wallace H. Clark
  • Meenhard Herlyn
Part of the Basic Life Sciences book series (BLSC, volume 57)


Melanocytes are distinctive cells in the basal layer of the epidermis, the choroid of the eye, certain mucous membranes, and the leptomeninges. Melanocytes arise during embryonal development from pluripotent cells migrating out of the neural crest. Functional maturation, i.e., the process by which cells express specific properties characteristic of the cell type, may progress in melanocytes through several, as yet undefined, stages (Fig. 1). Precursor cells for melanocytes (premelanocytes or melanoblasts) have been identified in human skin1, but these cells have been only preliminarily characterized. The phenotypic and functional characteristics of melanocytes are: a) melanin synthesis through the action of the tyrosinase enzyme; b) dendritic morphology; c) pigment donation to surrounding keratinocytes and d) no detectable proliferation in situ. Despite the undetectable proliferation, a stable 5–6:1 ratio between basal keratinocytes and melanocytes is maintained throughout the life of an individual suggesting a constant renewal of melanocytes.


Melanoma Cell Phorbol Ester Nerve Growth Factor Receptor Human Melanocyte Colony Form Efficiency 
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.

Abbreviations used are


alpha-melanocyte stimulating hormone


basic fibroblast growth factor; BPE, bovine pituitary extract


colony forming efficiency


epidermal growth factor


fetal calf serum


follicle stimulating hormone


isobutyl methyl xanthine


insulin-like growth factor


monoclonal antibody


melanocyte growth factor


melanocyte-stimulating growth activity


nerve growth factor


platelet derived growth factor


radial growth phase


12-0-tetradecanoyl phorbol-13-acetate


vertical growth phase


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    D. C. Bennet, K. Bridges, and I. A. McKay, Clonal separation of mature melanocytes from premelanocytes in a diploid human cell strain: Spontaneous and induced pigmentation of premelanocytes, J. Cell Sci. 77:167–183 (1985).Google Scholar
  2. 2.
    D. E. Elder and W. H. Clark, Jr., Developmental biology of malignant melanoma, in: “Pigment Cell”, Vol. 8, R. M. MacKie, ed., Karger, Basel (1987).Google Scholar
  3. 3.
    W. H. Clark, Jr., D. E. Elder, and M. Van Horn, The biologic forms of malignant melanoma, Hum. Pathol. 17:443–450 (1986).PubMedCrossRefGoogle Scholar
  4. 4.
    W. H. Clark, Jr., D. E. Elder, D. Guerry, IV, M. N. Epstein, M. H. Greene, and M. Van Horn, A study of tumor progression: the precursor lesions of superficial spreading and nodular melanoma, Hum. Pathol. 15:1147–1165 (1984).PubMedCrossRefGoogle Scholar
  5. 5.
    D. E. Elder, D. Guerry, IV, M. N. Epstein, L. Zehngebot, E. Lusk, M. Van Horn, and W. H. Clark, Jr. Invasive malignant melanomas lacking competence for metastasis, Am. J. Dermatopathol. 6:55–62 (1984).PubMedGoogle Scholar
  6. 6.
    M. Herlyn, M. L. Mancianti, J. Jambrosic, J. B. Bolen, and H. Koprowski, Regulatory factors that determine growth and phenotype of normal human melanocytes, Exp. Cell. Res. 179:322–331 (1988).PubMedCrossRefGoogle Scholar
  7. 7.
    M. Herlyn, W. H. Clark, U. Rodeck, M. L. Mancianti, J. Jambrosic, and H. Koprowski, Biology of tumor progression in human melanocytes, Lab. Invest. 56:461–474 (1987).PubMedGoogle Scholar
  8. 8.
    M. Herlyn, U. Rodeck, M. L. Mancianti, F. M. Cardillo, A. Lang, A. H. Ross, J. Jambrosic, and H. Koprowski, Expression of melanoma-associated antigens in rapidly dividing human melanocytes in culture, Cancer Res. 47:3057–3061 (1987).PubMedGoogle Scholar
  9. 9.
    M. Herlyn, D. Guerry, and H. Koprowski, Recombinant v-interferon induces changes in expression and shedding of antigens associated with normal human melanocytes, nevus cells, and primary and metastatic melanoma cells, J. Immunol. 134:4226–4230 (1985).PubMedGoogle Scholar
  10. 10.
    J. Thurin, M. Thurin, M. Herlyn, D. E. Elder, Z. Steplewski, W. H. Clark, Jr., and H. Koprowski. GD2 ganglioside biosynthesis is a distinct biochemical event in human melanoma tumor progression. FEBS Lett., 208:17–22 (1986).PubMedCrossRefGoogle Scholar
  11. 11.
    M. Herlyn, J. Thurin, G. Balaban, L. J. Bennicelli, D. Herlyn, D. E. Elder, E. Bondi, D. Guerry, P. C. Nowell, W. H. Clark, and H. Koprowski, Characteristics of cultured human melanocytes isolated from different stages of tumor progression, Cancer Res. 45:5670–5676 (1985).PubMedGoogle Scholar
  12. 12.
    M. L. Mancianti, M. Herlyn, D. Weil, J. Jambrosic, U. Rodeck, D. Becker, L. Diamond, W. H. Clark, and H. Koprowski, Growth and phenotypic characteristics of human nevus cells in culture. J. Invest. Dermatol. 90:134–141 (1988).PubMedCrossRefGoogle Scholar
  13. 13.
    G. Balaban, M. Herlyn, D. Guerry, R. Bartolo, H. Koprowski, W. H. Clark, and P. C. Nowell, Cytogenetics of human malignant melanoma and pre-malignant lesions, Cancer Genet. Cytogenet. 11:429–439 (1984).PubMedCrossRefGoogle Scholar
  14. 14.
    G. B. Balaban, M. Herlyn, W. H. Clark, Jr., and P. C. Nowell, Karyotypic evolution in human malignant melanoma, Cancer Genet. Cytogenet. 19:113–122 (1986).PubMedCrossRefGoogle Scholar
  15. 15.
    M. Herlyn, W. H. Clark, Jr., M. J. Mastrangelo, D. Guerry, IV, D. E. Elder, D. LaRossa, R. Hamilton, E. Bondi, R. Tuthill, Z. Steplewski, and H. Koprowski, Specific immunoreactivity of hybridoma-secreted monoclonal anti-melanoma antibodies to cultured cells and freshly derived human cells, Cancer Res. 40:3602–3609 (1980).PubMedGoogle Scholar
  16. 16.
    D. Guerry, IV, M. A. Alexander, D. E. Elder, and M. Herlyn, Interferon-Y regulates the T cell response to precursor nevi and biologically early melanoma, J. Immunol., 139:305–312 (1987).PubMedGoogle Scholar
  17. 17.
    R. Kath, U. Rodeck, J. Jambrosic, and M. Herlyn, Growth factor independence in vitro of primary melanoma cells from advanced but not early or intermediate lesions (Submitted for publication).Google Scholar
  18. 18.
    U. Rodeck, M. Herlyn, H. D. Menssen, R. W. Furlanetto, and H. Koprowski, Metastatic but not primary melanoma cells grow in vitro independently from exogenous growth factors, Int. J. Cancer 40:687–690 (1987).PubMedCrossRefGoogle Scholar
  19. 19.
    B. Westermark, A. Johnsson, Y. Paulsson, C. Betsholtz, C. H. Heldin, M. Herlyn, U. Rodeck, and H. Koprowski, Human melanoma cells lines of primary and metastatic origin express the genes encoding the chains of platelet-derived growth factor (PDGF) and produce a PDGF-like growth factor, Proc. Natl. Acad. Sci. USA 83:7197–7200 (1986).PubMedCrossRefGoogle Scholar
  20. 20.
    J. L. Bennicelli, J. Elias, J. Kern, and D. Guerry, IV, Production of interleukin 1 activity by cultured human melanoma cells, Cancer Res. (in press).Google Scholar
  21. 21.
    R. Halaban, B. S. Kwon, S. Ghosh, P. S. Delli Bovi, and A. Baird, bFGF as an autocrine growth factor for human melanomas, Oncogene Res. 3:177–186 (1988).PubMedGoogle Scholar
  22. 22.
    D. Moscatelli, M. Presta, J. Joseph-Silverstein, and D. B. Rifkin, Both normal and tumor cells produce basic fibroblast growth factor, J. Cell. Physiol. 129:273–276 (1986).PubMedCrossRefGoogle Scholar
  23. 23.
    A. Richmond, D. H. Lawson, D. W. Nixon, and R. K. Chawla, Characterization of autostimulatory and transforming growth factors from human melanoma cells, Cancer Res. 45:6390–6394 (1985).PubMedGoogle Scholar
  24. 24.
    M. Eisinger, O. Marko, S.-I. Ogata, and L. J. Old, Growth regulation of human melanocytes: Mitogenic factors in extracts of melanoma, astrocytoma, and fibroblast cell lines, Science 229:984–986 (1985).PubMedCrossRefGoogle Scholar
  25. 25.
    A. J. Linnenbach, K. Huebner, E. Premkumar Reddy, M. Herlyn, A. H. Parmiter, P. C. Nowell, and H. Koprowski, Structural alteration in the MYB protooncogene and deletion within the gene encoding α-type protein kinase C in human melanoma cell lines, Proc. Natl. Acad. Sci. USA 85:74–78 (1988).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Istvan Valyi-Nagy
    • 1
  • Ulrich Rodeck
    • 1
  • Roland Kath
    • 1
  • Maria Laura Mancianti
    • 1
  • Wallace H. Clark
    • 2
  • Meenhard Herlyn
    • 1
  1. 1.The Wistar Institute for Anatomy and BiologyPhiladelphiaUSA
  2. 2.The Pigmented Lesion ClinicUniversity of PennsylvaniaPhiladelphiaUSA

Personalised recommendations