A potent inhibitor of normal and transformed cell growth derived from contact-inhibited cells
Lipkin, G.; Knecht, M.E.; Rosenberg, M.
Cancer Research 38(3): 635-643
1978
ISSN/ISBN: 0008-5472 PMID: 626968 Document Number: 137440
Contact inhibition of growth (density-dependent regulation) is a form of in 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 previously restored 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) inhibited growth in vitro of a broad spectrum of malignant cell types of ectodermal, mesodermal and endodermal origin. Inhibition characterized by decreased saturation densities of cultures, growth in monolayers and individual cell enlargement was dose dependent, reversible and nontoxic at concentrations of < 100 .mu.g/ml. Neuroblastoma cells exhibited neurite differentiation. At higher concentrations (> 100-200 .mu.g/ml), MCIF was selectively lethal to malignant, noncontact-inhibited (compared to benign, contact-inhibited) 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 (MW about 160,000), was functionally identical with MCIF in 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 eventually provide a new class of cell surface-active agents for control of neoplastic growth.