Biochemical studies of a protein which restores contact inhibition of growth to malignant melanocytes

Abstract

A factor prepared from conditioned medium of a contact-inhibited hamster melanocytic cell line (FF), and which restores the capacity for contact inhibition of growth to malignant melanocytes, is a glycoprotein of molecular weight about 160000 whose amino acid composition shows an acid-base ratio of 2.04. Although the melanocyte contact inhibitory factor (MCIF) is a constituent of both contact-inhibited (FF) and non-contact-inhibited (RPMI 1846) melanocytes, being present in a fraction which includes endoplasmic reticulum and plasma membrane, it is spontaneously released only into culture media of the contact-inhibited (FF) cells. Addition of MCIF to cultures of highly malignant hamster melanocytes (RPMI 1846) is followed by a rapid fall of intracellular cGMP and rise in cAMP. A protein with electrophoretic mobility identical with that of MCIF is present in conditioned culture media of other contact-inhibited cell lines including a human epidermal line and human and mouse fibroblasts, but is absent from media of hamster melanoma, and much reduced in cultures of SV40-transformed mouse fibroblasts. MCIF may be a widely distributed growth regulatory macromolecule concerned with facilitating cell-cell interactions required for the generation and/or reception of normal signals leading to cessation of growth.