THE DESMOPLASTIC RESPONSE - INDUCTION OF COLLAGEN-SYNTHESIS BY MELANOMA-CELLS INVITRO

When cells from the human malignant melanoma cell line, UCT-Mel 7, were injected into athymic nude mice, tumours developed that were intensely infiltrated with fibrous tissue. In an attempt to reproduce this desmoplastic response in vitro, we co-cultured fibroblasts with UCT-Mel-7 cells, and observed a 2-fold increase in the rate of fibroblast collagen synthesis. This was associated with an increase in the amount of collagen mRNA present in co-cultured fibroblasts. The stimulation was both dose- and time-dependent, with maximal stimulation at a melanoma cell:fibroblast ratio of 1:1. Analysis of the kinetics of proline incorporation into collagen showed that co-culture affected the maximal rate of proline incorporation; no effect was observed on the concentration of proline required for 50% maximal collagen synthesis. The induction of fibroblast collagen synthesis showed an absolute requirement for close proximity between the fibroblasts and the melanoma cells. No soluble fibrogenic factor released by melanoma was detected.