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

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 Mg2+ 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 Mg2+ activity. However, maximizing contact between transformed cells at extremely high density stabilizes their plasma membrane, lowers their Mg2+ 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 Mg2+ regulation as the mechanism of normalization.