Membrane stabilization by intimate contact between cells reduces their Mg2+ activity and suppresses the neoplastic...

The mechanism of normalizing transformed cells by contact with normal cells is considered in relation to the mechanism of stimulating the growth of normal contact-inhibited cells. Stimulation is based on perturbation of the plasma membrane throughout the G1 period by growth factors. A primary effect of the membrane perturbation is a long-sustained increase of intracellular free Mg(2+) which increases the initiation frequency of polypeptide synthesis and accelerates the onset of DNA synthesis. Because the plasma membrane of transformed cells is kept in a continuously perturbed state and forms poor intercellular adhesions, it loses control of intracellular Mg(2+) activity. However, maximizing contact between transformed cells at extremely high density stabilizes their plasma membrane, lowers their Mg(2+) content and normalizes their phenotype. Normalization may also be obtained in contact with lower densities of quiescent, confluent normal cells. Evidence against a need for junctional communication supports membrane stabilization with restoration of Mg(2+) regulation as the mechanism of normalization.