TPA-resistance in Friend erythroleukemia cells: role of membrane lipid fluidity.

Summary Fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene was used to examine membrane lipid dynamics in clones of Friend erythroleukemia cells displaying sensitivity or resistance to the tumor promoting agent 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Two resistant clones yielded higher fluorescence anisotropy values, indicative of decreased lipid fluidity, as compared to two sensitive clones. This difference in fluorescence anisotropy was abolished by treatment of the sensitive clones with cholesteryl hemisuccinate. The treatment also removed another phenotypic difference between the sensitive and resistant clones. Cell adherence to plastic culture dishes in the presence of TPA, a property of sensitive but not of resistant clones, was markedly diminished when the former were enriched with the cholesteryl ester. No significant differences were observed in the binding of a phorbol ester to high affinity saturable receptors between sensitive versus resistant cells. These results implicate membrane lipids as determinants of the actions of phorbol ester tumor promoters.