Vasoactive intestinal peptide control of cyclic adenosine 3':5'-monophosphate levels in seven human colorectal adenocarcinoma cell lines in culture.

This study was undertaken to assess the role of vasoactive intestinal peptide (VIP) in the control of cyclic adenosine 3':5'-monophosphate production in colonic tumor cells. 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 cyclic adenosine 3':5'-monophosphate 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), by contrast, 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: (a) maximal responses were observed with 0.1 micro M VIP in both malignant and normal cells; (b) half-maximal responses were elicited by VIP concentrations in the 0.3 to 2 nM range in malignant cells (1.2 nM in normal cells), thus indicating the high apparent affinity of the cells to VIP; and (c) 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, in the order of 25, in normal cells. Secretin, a VIP agonist in intestinal tissue, stimulated cyclic adenosine 3':5'-monophosphate accumulation in all colorectal cells, but with a 1000- to 5000-fold lower potency than did VIP. These results show that the VIP-sensitive adenylate cyclase system operates in malignant as well as in normal colon epithelial cells.