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Induction of Melanoma Phenotypes in Human Skin by Growth Factors and Ultraviolet B

2004; American Association for Cancer Research; Volume: 64; Issue: 3 Linguagem: Inglês

10.1158/0008-5472.can-03-3438

1538-7445

Carola Berking, Richelle Takemoto, Kapaettu Satyamoorthy, Takahashi Shirakawa, Malihe Eskandarpour, Johan Hansson, P. VanBelle, David E. Elder, Meenhard Herlyn,

Immunotherapy and Immune Responses

Abstract Exposure to UV radiation likely plays a key role in melanoma development, whereas other etiologic agents remain unknown. Here we show that in normal human skin an increased expression of a combination of three growth factors, basic fibroblast growth factor, stem cell factor, and endothelin-3, along with exposure to UVB can transform normal melanocytes into a melanoma phenotype within 4 weeks. Invasion of melanoma lesions was found in skin from newborn donors, whereas melanomas in adult skin were of a noninvasive in situ type only. This suggests that susceptibility of skin to exogenous tumor promoters is dependent on age. This is the first report on human cancer initiation in vivo in which an imbalance of physiological factors combined with an environmental carcinogen can lead to transformation of normal tissue.