FGF expression allows nevus cells to survive in three-dimensional collagen gel under conditions that induce apoptosis in normal human melanocytes.
Melanocytes, the pigment forming cells of the skin, form an almost nonproliferating cell population located to the lowermost part of the epidermis. Normally melanocytes are not found higher in the epidermis or in the dermis. Nevi consist of melanocytes with altered growth characteristics and localization. The common pigmented nevus, a benign skin lesion, develops when melanocytes proliferate in the dermo-epidermal junction or in the dermis. Here we report growth characteristics of in vitro cultured normal human melanocytes and dermal nevus-derived melanocytes. As previously reported, nevus cells have a moderate to high FGF-2 expression level. Here we demonstrate that dermal nevus cells are able to survive in three-dimensional type 1 collagen culture, while normal human melanocytes rapidly undergo apoptosis. Melanocytes also, however, survive in collagen cultures in the presence of exogenous FGF-2. The survival of nevus cells in collagen is suppressed by protamine, an inhibitor of FGF-mediated cell stimulation. The in vivo growth environment of dermal nevus cells consists largely of type I and type III collagens. The results suggest that FGF-2 expression by nevus cells allows them to adapt to grow in the dermis. FGF-2 obviously has importance as a melanocyte survival factor and probably also in the development of malignant melanoma.
Department of Virology, Haartman Institute, University of Helsinki, Finland.
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Alanko
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Rosenberg
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Saksela
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D005353:Fibronectins / Q000494:pharmacology; D005782:Gels; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009506:Nevus / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
D005353:Fibronectins; D005782:Gels; D007797:Laminin; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D003094:Collagen