Overexpression of m-calpain in human colorectal adenocarcinomas.
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.


CONCLUSIONS
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.
Lakshmikuttyamma
Ashakumary
A
Department of Pathology, College of Medicine, University of Saskatchewan, 20 Campus Drive, Saskatoon, Canada S7N 4H4.
Selvakumar
Ponniah
P
Kanthan
Rani
R
Kanthan
Selliah Chandra
SC
Sharma
Rajendra K
RK
D000230:Adenocarcinoma / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002135:Calcium-Binding Proteins / Q000494:pharmacology; D002148:Calmodulin-Binding Proteins / Q000494:pharmacology; D002154:Calpain / Q000096:biosynthesis* / Q000235:genetics* / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000235:genetics*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry
D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D002148:Calmodulin-Binding Proteins; D015853:Cysteine Proteinase Inhibitors; C033668:calpastatin; D002154:Calpain; C449000:m-calpain