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.
Bonfil
R D
RD
Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA 19111.
Momiki
S
S
Fridman
R
R
Reich
R
R
Reddel
R
R
Harris
C C
CC
Klein-Szanto
A
A
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002633:Chemotaxis / Q000187:drug effects; D004075:Diglycerides / Q000494:pharmacology*; D004848:Epithelium; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D008168:Lung; D051379:Mice; D008819:Mice, Nude; D003012:Microbial Collagenase / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009368:Neoplasm Transplantation; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014132:Trachea / Q000637:transplantation; D014183:Transplantation, Heterologous
D004075:Diglycerides; D005989:Glycerides; C044295:1,2-dioctanoylglycerol; D003012:Microbial Collagenase; D013755:Tetradecanoylphorbol Acetate