TGF‐β 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‐β cell‐surface receptors, the response to exogenous TGF‐β₁ and the autocrine production of TGF‐β in normal and squamous cell carcinoma‐derived human oral keratinocytes with variable degrees of cellular differentiation. TGF‐β receptor expression, the response to exogenous ligand and the autocrine production of TGF‐β appeared unrelated to cellular differentiation. Cells expressed variable proportions of type‐I,‐II and‐III TGF‐β receptors. The expression of type‐III receptors correlated inversely with the expression of type‐I receptors, but there was no relationship between type‐II and either type‐I or type‐III TGF‐β receptors. Normal cells and the majority (7 of 8) of tumour‐derived keratinocytes were inhibited by exogenous TGF‐β₁ and the degree of inhibition correlated with the expression of type‐I, but not type‐II or type‐III, TGF‐β receptors. One tumour‐derived cell line was refractory to exogenous TGF‐β₁ although it expressed all 3 receptor types. Endogenous TGF‐β was produced by both normal and tumour‐derived keratinocytes and correlated inversely to the expression of type‐I, but not type‐II, TGF‐β receptors. Further, cells that produced more autocrine TGF‐β had a diminished response to exogenous TGF‐β₁. The data indicate a complex interaction between the expression of TGF‐β cell‐surface receptors, endogenous ligand production and the cellular response to exogenous TGF‐β₁.