Caveolin-1 levels are down-regulated in human colon tumors, and ectopic expression of caveolin-1 in colon carcinoma cell lines reduces cell tumorigenicity

Caveolin-1 expression and function were investigated in human colon cancer. Low levels of caveolin-1 mRNA and protein were detected in several colon c arcinoma cell lines. Moreover, caveolin-1 protein levels were significantly reduced in human tumor epithelial mucosa (3.6 +/- 1.4-fold) when compared with normal colon mucosa for a majority (10 of 15) of the patients characte rized. To directly assess the role of caveolin-1 in tumor development, cave olin-1 was reexpressed in the HT29 and DLD1 colon carcinoma cells, and the resulting HT29-cav-1 or DLD1-cav-1 cells were tested for tumorigenicity in nude mice. In most experiments, tumor formation was either blocked or retar ded for HT29-cav-1 cells (10 of 13 mice) and DLD1-cav-1 cells (5 of 7 mice) , as compared with both mock-transfected and parental HT29 or DLD1 cells. I nterestingly, basal caveolin-1 levels were significantly reduced in HT29-ca v-1 and DLD1-cav-1 cells isolated from tumors. Likewise, endogenous caveoli n-1 mRNA and protein levels were found to be reduced in NIH-3T3 cells recov ered from tumors after injection into nude mice. Thus, reexpression of cave olin-1 in colon carcinoma lines reduced the probability of tumor formation in vivo, and when tumors did develop from either HT29-cav-1, DLD1-cav-1, or NIH-3T3 cells, lower basal levels of caveolin-1 were detected, Finally, ev idence was obtained indicating that initial caveolin-1 down-regulation in c olon cancer cells need not be an entirely irreversible process because cell survival on selection for either drug resistance or increased metastatic p otential correlated with increased caveolin-1 expression levels.