Cysteine endopeptidase activity levels in normal human tissues, colorectal adenomas and carcinomas

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Abstract
We have assayed cysteine endopeptidase activities in 17 types of normal human tissue and in matched sets of colorectal mucosa, adenoma and carcinoma samples. Our data indicate that cathepsin B enzyme levels vary 70‐fold and cathepsin L enzyme levels vary 20‐fold from one normal tissue to another. Cathepsin B specific activity in normal tissues fell into 3 categories. High activity, with a mean of 156.7 ± 41.5 nmoles min−1 mg−1 protein, was measured in liver, thyroid, kidney and spleen; intermediate activity, with a mean of 60.2 ± 8.3 nmoles min−1 mg−1 protein, was measured in heart, colon, adrenal and lung; and low activity, with a mean of 18.4 ± 9.7 nmoles min−1 mg−1 protein, was measured in prostate, testis, nerve, stomach, pancreas, brain, skeletal muscle, skin and breast. Cathespin L specific activity fell into 2 categories. High activity, with a mean of 51.1 ± 4.9 nmoles min−1 mg−1 protein, was measured in thyroid, liver and kidney; and low activity, with a mean of 11.4 ± 5.5 nmoles min−1 mg−1 protein, was measured in spleen, colon, heart, adrenal, lung, testis, brain, nerve, skin, stomach, pancreas, skeletal muscle, prostate and breast. Our characterization of these enzyme levels provides a reference standard for normal cathepsin B and L activities in human tissues that should enhance the detection of their deregulation in disease states. For example, in studies of colorectal carcinoma and normal mucosa, we observed a significant tumor‐specific increase in cathepsin B and L activities with particularly high activity levels in earlier (Dukes′ A and B) compared to later (Dukes′ C and D) stages of colorectal cancer. In contrast, adenomas from colorectal cancer patients expressed normal levels of cathepsin B activity, providing evidence that the increase in expression of cathepsin B may be a sensitive marker for progression from the pre‐malignant to the malignant state in the development of colorectal cancer.