[Frontiers in Bioscience 3, d1005-1010, September 15, 1998] |
MOLECULAR EVENTS IN MELANOMA DEVELOPMENT AND PROGRESSION
Friedegund Meier1, Kapaettu Satyamoorthy1, Mark Nesbit1, Mei-Yu Hsu1, Birgit Schittek2, Claus Garbe2, and Meenhard Herlyn1
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 191041, Department of Dermatology, University of Tuebingen, Liebermeisterstr.25, 72076 Tuebingen, Germany2
Received 7/17/98 Accepted 8/10/98
7. SUMMARY AND PERSPECTIVES
Melanomas can develop in a sequence of steps which have been clinically and histologically defined. The very first step from a normal cell to a benign lesion appears to be an event not dictated by genetic alterations. Instead melanocytes escape from keratinocytes through loss of E-cadherin expression. At that time, cells must receive a genetic "hit" in order to progress, and then cytological and architectural atypia may follow. The nature of these changes remains to be elucidated. The dysplastic cells can persist for years before they begin to proliferate to form RGP. At the transition from RGP to VGP, one or more genetic hits must occur. Cells then begin to proliferate more rapidly and develop stroma and undergo angiogenesis. Changes in adhesion receptor expression and function further accelerate progression. The final step, metastasis, is dictated by endogenous oncogenes and tumor suppressor genes, and by exogenous interactions with the host. Metastatic cells have a highly unstable phenotype and can rapidly adapt to selective pressure, allowing the cells to survive even under the most unfavorable circumstances. Future studies to further dissect each step of melanoma progression should lead to the development of more specific and effective therapies.