Clusterin a potential biomarker of colon cancer

A glycoprotein, clusterin, is a “potential contributor to the set of biomarkers for early detection of human colon cancer,” researchers report in the July 28th early edition of Proceedings of the National Academy of Sciences.

In an attempt to identify candidate tumor-associated markers, Dr. William F. Dove from the University of Wisconsin in Madison and colleagues used cDNA subtraction to compare gene expression patterns in mice that develop intestinal tumors and in tumor-free mice. One “prominent” candidate biomarker, clusterin, was identified. The protein was discovered 20 years ago, but its function is not yet known.The association with colon cancer was then tested in a series of validation steps. “In situ hybridization and immunohistochemistry were used to analyze clusterin expression at a cellular level on a series of murine intestinal and human colonic neoplasms,” the investigators explain. “Clusterin passed the test,” Dr. Dove told Reuters Health. It was upregulated in both early and late intestinal neoplasms in the mouse and in early intestinal lesions in humans. Most but not all tumor cells with high clusterin levels lacked differentiation markers, suggesting that clusterin cannot serve as a solo marker for intestinal tumors, the team says. Elevated clusterin was also strongly associated with loss of adenomatous polyposis coli (Apc) antigen. “Loss of tumor suppressor Apc function initiates tumorigenesis in the intestine,” they explain. Low clusterin levels were found in tumor cells undergoing apoptosis. “We believe that the identification of molecular signatures of colon cancer is one route leading to early detection,” Dr. Dove told Reuters Health. “In the case of colon cancer, early detection can provide for a major reduction in disease burden because surgery to remove local cancerous lesions is usually curative.” He added, “Clusterin and other tumor-associated molecules are now being subjected to further validation as to their usefulness in the clinic for early detection and diagnosis.” (Source: Proc Natl Acad Sci USA 2003: Reuters Health: Megan Rauscher: July 29, 2003: Oncolink)