Differential expression and function of caveolin-1 in human gastric cancer progression.

Caveolin-1 is a scaffold protein of caveolae that acts as a tumor modulator by interacting with cell adhesion molecules and signaling receptors. The role of caveolin-1 in the pathogenesis of gastric cancer (GC) is currently unknown. We show by confocal immunofluorescence microscopy and immunohistochemistry of biopsies from GC patients (n = 41) that the nonneoplastic mucosa expressed caveolin-1 in foveolar epithelial cells and adjacent connective tissue. GC cells of only 3 of 41 (7%) patients expressed caveolin-1 and were all of the intestinal type. Quantitative PCR and Western blotting confirmed that, compared with nonneoplastic tissue, the overall caveolin-1 mRNA was decreased in 14 of 19 (74%) GC patients and protein in 7 of 13 (54%), respectively. Strong caveolin-1 reactivity was found in the nonepithelial compartment (myocytes, fibroblasts, perineural, and endothelial cells) in both tumor-free and GC samples. In a series of human GC cell lines, caveolin-1 expression was low in cells derived from a primary tumor (AGS and SNU-1) but was increased in cell lines originating from distant metastases (MKN-7, MKN-45, NCI-N87, KATO-III, and SNU-5). Ectopic expression of caveolin-1 in AGS cells decreased proliferation but promoted anchorage-independent growth and survival. RNAi-mediated knockdown of endogenous caveolin-1 in MKN-45 cells accelerated cell growth. These data indicate that caveolin-1 exhibits a stage-dependent differential expression and function in GC and may thereby contribute to its pathogenesis.