Response to growth factors of human dermal fibroblasts in a quiescent state owing to cell-matrix contact inhibition.

Mitogenic responses to various growth factors were compared for quiescent human dermal fibroblasts cultured under three different conditions; serum depletion, cell-cell contact inhibition and cell-matrix contact inhibition. The non-dividing fibroblasts cultured under a low serum condition (0.2% fetal bovine serum, FBS) or in a confluent culture with 10% FBS resumed multiplying upon exposure to any one of or any combination of the growth factors examined; epidermal growth factor (EGF), basic fibroblast growth factor (b-FGF), platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta). The only exception was the lack of effect of TGF-beta on the cell under a low serum condition. In contrast, the proliferation of fibroblasts which were growth-arrested in contracted collagen gel by cell-matrix contact inhibition was not stimulated by any of the growth factors examined except for PDGF. It is currently accepted that the mechanism of growth stimulation or signal transduction after binding of each growth factor to the specific receptor depends on the kind of growth factor. The results suggest that the signal transductions delivered by EGF, b-FGF or TGF-beta are inactivated by a high level of interaction of collagen fibrils with the cell membrane (under the condition of cell-matrix contact inhibition); whereas the signal transduction by PDGF is unaffected. The finding supports the existence of a specific growth stimulation pathway for PDGF.