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.
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D004075:Diglycerides / Q000494:pharmacology; D004224:Diterpenes; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D009362:Neoplasm Metastasis; D010703:Phorbol Esters / Q000494:pharmacology; D010704:Phorbols / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000494:pharmacology
D004075:Diglycerides; D004224:Diterpenes; D008934:Mitogens; D010703:Phorbol Esters; D010704:Phorbols; D013729:Terpenes; C011309:mezerein; C038237:1-oleoyl-2-acetylglycerol; D011494:Protein Kinases; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate