Tumor-promoter-enhanced destruction of noninvasive human benign colon tumor cells by cocultivated carcinoma cells.
Colon carcinoma cells are first found as microscopic foci within benign tumors or adenomas. The carcinoma must invade the adenoma which protrudes into the colon lumen before it can infiltrate the bowel wall. A quantitative model for this process has been developed in tissue culture in which human colon carcinoma cells destroy cocultivated adenoma colonies. 43 adenoma colonies were assayed by cocultivation with carcinoma cells. Constitutive secretion of the urokinase form of plasminogen activator by carcinoma cells apparently plays some role in adenoma destruction as inhibition of this protease by the competitive inhibitor benzamidine reversibly inhibited adenoma destruction (p less than 0.01). Elevation of plasminogen activator secretion by addition of the tumor promoter 12-tetradecanoylphorbol-13-acetate significantly enhanced the destruction of colonies cultured from tubular adenomas with only mild dysplasia (p less than 0.025) and from villous, villotubular and tubular adenomas with moderate to severe dysplasia (p less than 0.0005).
Friedman
E A
EA
Laboratory of Gastrointestinal Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, N.Y.
Buset
M
M
Winawer
S J
SJ
D000236:Adenoma / Q000378:metabolism / Q000473:pathology*; D002273:Carcinogens / Q000494:pharmacology*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D003110:Colonic Neoplasms / Q000473:pathology*; D006801:Humans; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D002273:Carcinogens