Modulation of cell growth by retinoids and their possible mechanisms of action

Retinoids can enhance or inhibit anchorage-dependent and -independent cell growth of many different cell types in vitro. The action is dependent on the concentration of the retinoid, the cell line, and culture conditions. Inhibition of cell growth by retinoids is accompanied by a reduction in ornithine decarboxylase activity and an accumulation of cells in the G1 phase of the cell cycle. Whether the action on this enzyme is the cause or the effect of the restriction in G1 has yet to be determined. It is clear that retinoids can serve as growth-promoting agents of certain eukaryotic cells and should be included in tests to optimize cell culture conditions in serum-free medium. Retinoids can act synergistically with a large number of growth factors. Retinoids enhance the binding of epidermal growth factor (EGF) to a variety of cell lines. These compounds increase the number of available receptor sites but do not have a marked effect on the affinity of EGF to its receptor. The enhancement of cell growth by retinoids may be due, at least in part, to this increase in EGF binding. The presence of retinoid-binding proteins does not correlate with the action of retinoids on cell growth, which indicates that these binding proteins are not essential in the modulation of cell growth in vitro. It remains to be established whether the influence of retinoids on cell growth is mediated by alterations in cell surface properties induced either directly by changes in, for example, physicochemical properties of the membrane or indirectly via the formation of retinylphosphate mannose intermediates.