VASOACTIVE INTESTINAL PEPTIDE CONTROL OF CYCLIC ADENOSINE 3'-5'-MONOPHOSPHATE LEVELS IN 7 HUMAN COLORECTAL ADENOCARCINOMA CELL-LINES IN CULTURE

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (7) , 2529-2533
Abstract
The role of vasoactive intestinal peptide (VIP) in the control of cyclic[c]AMP production in colonic tumor cells was studied. Seven human colorectal adenocarcinoma cell lines in culture were investigated (HT-29, HRT-18, SW-480, Caco-2, CO-115, CO-125 and HCT-8R). These cell-lines had a cAMP production system which was very sensitive to VIP but less so to prostaglandin E1 and/or isoproterenol. Nonintestinal human malignant epithelial cells, such as HeLa (cervix) and Caki-1 and Caki-2 (kidney), did not respond to VIP. The dose-response relationships of malignant colorectal cells were compared to those obtained with epithelial cells of normal human colon and showed that: maximal responses were observed with 0.1 .mu.M VIP in malignant and normal cells; half-maximal responses were elicited by VIP concentrations in the 0.3-2 nM range in malignant cells (1.2 nM in normal cells), thus indicating the high apparent affinity of the cells to VIP; and the magnitudes of the responses (stimulated:basal ratios) were highly variable in malignant cells, ranging from 225 in HT-29 cells to 3.5 in Caco-2 cells, but were more constant, on the order of 25, in normal cells. Secretin, a VIP agonist in intestinal tissue, stimulated cAMP accumulation in all colorectal cells, but with a 1000- to 5000-fold lower potency than did VIP. The VIP-sensitive adenylate cyclase system operates in malignant as well as in normal colon epithelial cells.