A potent inhibitor of normal and transformed cell growth derived from contact-inhibited cells.

Contact inhibition of growth (density-dependent regula tion) is a form ofm vitro growth control, the loss of which is correlated with in vivo tumorigenicity. A diffusible factor prepared from culture medium of a contact-inhibited line of hamster melanocytes has previously been found to restore the capacity for contact inhibition of growth to malignant melanocytes of man, mouse, and hamster, while also producing characteristic morphological changes. In the present studies the species specificity of the growth inhibitory effect was examined. The melanocyte contact inhibitory factor (MCIF) was found to inhibit growth in vitro of a broad spectrum of malignant cell types of ectoderma!, mesoderma!, and endoderma! origin. Inhi bition characterized by decreased saturation densities of cultures, growth in monolayers, and individual cell en largement was dose dependent, reversible, and nontoxic at concentrations of 100 jug/ml. Neuroblastoma cells exhibited neurite differentiation. At higher concentrations (100 to 200 /¿g/ml), MCIF was selectively lethal to malig nant, non-contact-inhibited (compared to benign, contactinhibited) cell types. A fraction analogous to MCIF, prepared from culture medium of a line of contact-inhibited human epidermal cells and containing a protein electrophoretically identical with the major protein present in MCIF (M.W. about 160,000), was functionally identical with MCIF in both morphological and growth inhibitory effects on malignant melanocytes. The growth regulatory macromolecular component(s) produced by contact-inhibited cells is able to restore some aspects of cell surface-mediated in vitro growth control to malignant cells. Such components may even tually provide a new class of cell surface-active agents for control of neoplastic growth.