Increased expression of carbonic anhydrase-related protein (CA-RP) VIII has previously been shown in colorectal carcinoma. Since CA-RP has no catalytic carbonic anhydrase (CA) activity, the present study attempted to elucidate its biological significance in colon cancer cells. From a colon cancer cell line (LoVo), we established clones that overexpressed CA-RP VIII (LoVo-CA8) and a control transfectant with a vector alone (LoVo-pCIneo) and studied alterations in the biological behaviors of the tumor cells both in vitro and in vivo. LoVo-CA8 cells showed significantly increased mRNA and protein expressions of CA-RP VIII as compared to LoVo-pCIneo cells. Cell proliferation, colony formation, and cell invasion assays showed that LoVo-CA8 cells had significantly higher cell proliferative and invasive abilities as compared to parental LoVo and LoVo-pCIneo cells in vitro. In an in vivo xenograft assay, LoVo-CA8 cells showed a higher tumor growth rate than parental LoVo cells. Further, small interfering RNA (siRNA)-mediated knockdown of CA-RP VIII revealed significant inhibition in cell proliferation and colony formation of a colon cancer cell line HCT116, which showed high endogenous expression of CA-RP VIII. These findings indicated that CA-RP VIII plays a role in the growth of colon cancer cells.
(c) 2007 Wiley-Liss, Inc.