Induction of Human Fibroblast Proliferation by Epidermal Growth Factor (EGF): Enhancement by an EGF-Binding Arginine Esterase and by Ascorbate

The effect of mouse epidermal growth factor (mEGF) and an mEGF-binding arginine esterase on the growth of cultured human fibroblasts has been studied. Physiological concentrations (10-9-10-10 M) of the growth factor were found to stimulate DNA replication and cell proliferation in quiescent cultures, and the arginine esterase, which is normally associated with mEGF in vivo, was shown to enhance 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 was found to elicit 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.