To identify molecules to serve as diagnostic markers for renal cell carcinoma (RCC) and as targets for novel therapeutic drugs, we investigated genome-wide expression profiles of RCCs using a cDNA microarray. We subsequently confirmed that C6776 was expressed exclusively in RCCs and fetal kidney. Induction of C6776 cDNA into COS7 cells led to secretion of the gene product into culture media and resulted in enhancement of cell growth. Small interfering RNA (siRNA) effectively inhibited expression of C6776 in human RCC cells that endogenously expressed high levels of the protein, and significantly suppressed cell growth. Moreover, addition of polyclonal anti-C6776 antibody into culture media induced apoptosis in RCC-derived cell lines. By binding to an extracellular domain of a frizzled receptor, C6776 protein enhanced oncogenic Wnt-signaling and its own transcription, suggesting that this product is likely to function as an autocrine growth factor. ELISA analysis of clinical samples identified secretion of C6776 protein into the plasma of RCC patients even at an early stage of tumor development, whereas it was detected at significantly lower levels in healthy volunteers or patients with chronic glomerulonephritis. The combined evidence suggests that this molecule represents a promising candidate for development of molecular-targeting therapy and could serve as a prominent diagnostic tumor-marker for patients with renal carcinomas.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]