TGF-BETA RECEPTOR REGULATION MEDIATES THE RESPONSE TO EXOGENOUS LIGAND BUT IS INDEPENDENT OF THE DEGREE OF CELLULAR-DIFFERENTIATION IN HUMAN ORAL KERATINOCYTES

This study examined the expression of TGF-beta cell-surface receptors, the response to exogenous TGF-beta(1) and the autocrine production of TGF-beta in normal and squamous cell carcinoma-derived human oral ker atinocytes with variable degrees of cellular differentiation. TGF-beta receptor expression, the response to exogenous ligand and the autocri ne production of TGF-beta appeared unrelated to cellular differentiati on. Cells expressed variable proportions of type-I, -II and -III TGF-b eta receptors. The expression of type-III receptors correlated inverse ly with the expression of type-I receptors, but there was no relations hip between type-II and either type-III TGF-beta receptors. Normal cel ls and the majority (7 of 8) of tumour-derived keratinocytes were inhi bited by exogenous TGF-beta(1) and the degree of inhibition correlated with the expression of type-I, but not type-II or type-III, TGF-beta receptors. One tumour-derived cell line was refractory to exogenous TG F-beta(1) although it expressed all 3 receptor types. Endogenous TGF-b eta was produced by both normal and tumour-derived keratino-cytes and correlated inversely to the expresson of type-I, but not type-II, TGF- beta receptors. Further, cells that produced more autocrine TGF-beta h ad a diminished response to exogenous TGF-beta(1). he data indicate a complex interaction between the expression of TGF-beta cell-surface re ceptors, endogenous ligand production and the cellular response to exo genous TGF-beta(1). (C) 1994 Wiley-Liss, Inc.