THE MITOGENIC EFFECT OF KGF AND THE EXPRESSION OF ITS CELL-SURFACE RECEPTOR ON CULTURED NORMAL AND MALIGNANT HUMAN ORAL KERATINOCYTES AND ON CONTIGUOUS FIBROBLASTS

This study examined the mitogenic response to keratinocyte growth fact or (KGF) of normal and tumour-derived human oral keratinocytes in whic h the degree of cellular differentiation was known and in contiguous f ibroblast cultures derived from the malignant epithelial cultures. Ker atinocytes, but not fibroblasts, were stimulated by KGF, thereby demon strating epithelial target cell specificity of the ligand. KGF-induced stimulation of the tumour-derived keratinocytes cultured in the absen ce of the 3T3 fibroblast support broadly correlated with the degree of cellular differentiation; well-differentiated keratinocytes were stim ulated more by KGF than their less differentiated counterparts. Malign ant oral keratinocytes expressed KGF cell surface receptors (K-D 451-7 09 pM; receptors/cell 2306-13645), but KGF receptor mRNA did not corre late with either KGF-induced mitogenesis or the degree of epithelial c ell differentiation. When the tumour-derived keratinocytes were cultur ed in the presence of 3T3 fibroblasts, the mitogenic response to KGF w as comparable to normal epithelial cells. The results suggest that KGF -mediated growth stimulation may not be significant in providing a sel ective advantage for the growth of malignant keratinocytes.