Influence of cultured dermal fibroblasts on human melanoma cell proliferation, matrix metalloproteinase-2 (MMP-2) expression and invasion in vitro.

The dermis is the main site of melanoma invasion. Matrix metalloproteinases (MMPs), especially MMP-2, produced by melanoma or surrounding stromal cells, are essential for the destruction of dermal extracellular matrix. Here, we examined how dermal fibroblasts influenced proliferation, MMP-2 secretion and invasion of human melanoma cell lines in vitro. Human melanoma cell lines M3 Da and M1Dor were cocultured with dermal fibroblasts under non-contact and contact conditions in order to assess both soluble and insoluble factors, respectively. Zymographic analysis showed that the levels of MMP-2 and TIMP-2 in melanoma cells were not altered in non-contact cocultures when compared with those in individual cultures. However, in contact cocultures, the expression of MMP-2 in membrane extracts was enhanced. Under our coculture conditions, dermal fibroblasts failed to upregulate melanoma cell invasion through a three-dimensional type I collagen matrix. Since stromal and cancer cell contacts have been shown to occur after disruption of the extracellular matrix, we hypothesized that fibroblasts may influence melanoma cell invasion after the beginning of tumor progression through the dermis.