Human melanoma progression in skin reconstructs - Biological significance of bFGF

Human skin reconstructs are three-dimensional in vitro models consisting of epidermal keratinocytes plated onto fibroblast-contracted collagen gels. C elts in skin reconstructs more closely recapitulate the in situ phenotype t han do cells in monolayer culture. Normal melanocytes in skin reconstructs remained singly distributed at the basement membrane which separated the ep idermis from the dermis. Cell lines derived from biologically early primary melanomas of the radial growth phase proliferated in the epidermis and the basement membrane was left intact Growth and migration of the radial growt h phase melanoma cells in the dermal reconstruct and tumorigenicity in vivo were only observed when cells were transduced with the basic fibroblast gr owth factor gene, a major autocrine growth stimulator for melanomas. Primar y melanoma cell lines representing the more advanced stage vertical growth phase invaded the dermis in reconstructs and only an irregular basement mem brane was formed. Metastatic melanoma cells rapidly proliferated and aggres sively invaded deep into the dermis, with each cell line showing typical in vasion and growth characteristics. Our results demonstrate that the growth patterns of melanoma cells in skin reconstructs closely correspond to those in situ and that basic fibroblast growth factor is critical for progressio n.