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Overexpression of m-Calpain in Human Colorectal Adenocarcinomas

Departments of ¹ Pathology and ² Surgery, College of Medicine, University of Saskatchewan, and ³ Cancer Research Unit, Health Research Division, Saskatchewan Cancer Agency, Saskatoon, Saskatchewan, Canada

Requests for reprints: Rajendra K. Sharma, Department of Pathology, College of Medicine, University of Saskatchewan, and Cancer Research Unit, Health Research Division, Saskatchewan Cancer Agency, 20 Campus Drive, Saskatoon, Saskatchewan, Canada S7N 4H4. Phone: 306-966-7733; Fax: 306-655-2635. E-mail: rsharma{at}scf.sk.ca

Background: Calpains represent a well-conserved family of Ca²⁺-dependent proteolytic enzymes. Recently, the importance of calpain in the metastatic process has received great attention. To investigate whether m-calpain contributes to the pathogenesis of colorectal cancer, we investigated the expression of m-calpain and its inhibitors, calpastatin and high-molecular-weight calmodulin-binding protein (HMWCaMBP), in human colorectal surgical specimens. Methods: Fifty cases of colon carcinoma were evaluated for this study. Of 50 cases evaluated, we presented in this report six cases for m-calpain, calpastatin and HMWCaMBP protein expression by Western blot analyses was done in both normal and invasive tumor components of human samples. In addition, immunohistochemistry analysis was also carried out in all patients. Results: The activity and protein expression of m-calpain was significantly higher in colorectal adenocarcinoma than in normal colonic mucosa. This finding was corroborated by immunohistochemical studies that showed strong cytoplasmic staining in the colon tumors with m-calpain antibody. The decreased expression of these calpain inhibitors (calpastatin and HMWCaMBP) paralleled increased activity and expression of calpain in colorectal adenocarcinoma and the well-documented involvement of this Ca²⁺-dependent protease in colon tumor. Conclusion: Increased activity and moderate staining of m-calpain in polyps show the usage of this enzyme as a marker for the early detection of colorectal adenocarcinoma using immunologic approaches. These findings represent the first description of calpain overexpression in colorectal cancer. This has implications with regard to the design of chemotherapeutic drugs as well as in monitoring colorectal cancer in early stages of the metastatic process.

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