Enhancement of the invasive ability of a transformed human bronchial epithelial cell line by 12-O-tetradecanoyl-phorbol-13-acetate and diacylglycerol.

The effect of the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was studied using an immortalized human bronchial epithelial cell line, BEAS-2B, both in vivo and in vitro. The in vivo model consisted of tracheas reconstituted with an epithelium of BEAS-2B cells xenotransplanted into athymic nude mice. Intraluminal TPA treatment caused increased BEAS-2B cell proliferation and downgrowth into the tracheal stroma. In an in vitro invasion assay, TPA enhanced the invasive capacity of BEAS-2B cells 20- to 25-fold. A similar result was observed with diacylglycerol (DAG), an endogenous activator of protein kinase C, and the effects of TPA and DAG were abolished by simultaneous treatment with H-7, a protein kinase C inhibitor. TPA induced type IV collagenolysis, and this effect also was prevented by H-7. These data are consistent with the hypothesis that TPA causes these cells to become invasive by inducing collagenase activity and that this effect is mediated via protein kinase C.