Induction of human fibroblast proliferation by epidermal growth factor (EGF): enhancement by an EGF-binding arginine esterase and by ascorbate.

Abstract

The effect of mouse epidermal growth factor (mEGF) and in mEGF-binding arginine esterase on the growth of cultured human fibroblasts was studied. Physiological concentrations (10-9-10-10 M) of the growth factor stimulate a DNA replication and cell proliferation in quiescent cultures; the arginine esterase, which is normally associated with mEGF in vivo, enhanced this growth effect synergistically. The cellular response to mEGF was dependent upon a low, growth-limiting concentration of serum in the extracellular medium. Ascorbic acid, which alone exhibited no growth-promoting effect, could partially replace this requirement, and elicited a rapid and marked increase in proline hydroxylation. Quiescent cultures in serum-free medium containing ascorbic acid were stimulated by the combination of mEGF and the esterase in a manner comparable to that achieved with serum shift-up. The possible requirement of a collagen-containing extracellular matrix for the growth response to mEGF is discussed.