Comparative localization of cathepsin B protein and activity in colorectalcancer

Cathepsin B is a lysosomal cysteine proteinase that may participate in canc er progression. We compared localization of its protein and activity during progression of human colorectal cancer. In adenomas and carcinomas, protei n expression and, particularly, activity were elevated compared with those in normal colorectal mucosa. In normal mucosa, cathepsin B protein expressi on was moderate in stroma and variable in epithelium, whereas activity was mainly present in distinct areas of stroma directly underneath the surface of the colon and in epithelium at the surface of the colon. Stroma in adeno mas and carcinomas contained moderate to high protein levels but little act ivity except for areas of angiogenesis, inflammation, and necrosis, in whic h activity was high. In adenomas and the majority of well-differentiated ca rcinomas and moderately differentiated carcinomas, cathepsin B protein and activity were found in granular form in the epithelium, close to the baseme nt membrane. Protein and activity levels were low and diffusely distributed in cancer cells in the remainder of the well-differentiated and moderately differentiated carcinomas and in all poorly differentiated carcinomas. Inv asive fronts in most cancers contained moderate protein levels but high act ivity. We conclude that (a) activity localization is essential to understan d the role of cathepsin B in cancels progression, and (b) cathepsin B activ ity in human colon is associated with invasion of cancer cells, endothelial cells, and inflammatory cells, and in cell death, both apoptotic and necro tic.