Effects of 12-O-tetradecanoylphorbol-13-acetate on adhesiveness and lung-colonizing ability of Lewis lung carcinoma cells.

The potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) enhanced the adherence of low-metastatic Lewis lung carcinoma cells (P-29) to the surface of plastic culture dishes and to monolayers of endothelial cells. This effect was transient, being apparent within 15 min and maximal within 1 h after treatment with TPA. Biologically active analogues of TPA and mezerein also enhanced attachment of P-29 cells, whereas inactive analogues of TPA did not. TPA-treated P-29 cells formed many more pulmonary nodules than did untreated P-29 cells when injected i.v. into C57BL/6 mice. The kinetics of enhancement of attachment of P-29 cells after TPA treatment coincided well with that of enhancement of their lung-colonizing ability. Addition of TPA to P-29 cells stimulated phosphorylation of a cellular protein with a molecular weight of 54,000. The possibility that this phosphorylation was related to activation of Ca2+ phospholipid-dependent protein kinase was suggested by the fact that phospholipid breakdown induced by exogenous treatment of the cells with Clostridium perfringens phospholipase C and 1-oleoyl-2-acetylglycerol also enhanced Mr 54,000 cellular protein phosphorylation. However, neither phospholipase C nor 1-oleoyl-2-acetylglycerol enhanced attachment of P-29 cells or their lung-colonizing ability.