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Journal of Histochemistry and Cytochemistry, Vol. 48, 1421-1430, October 2000, Copyright © 2000, The Histochemical Society, Inc.

ARTICLE

Comparative Localization of Cathepsin B Protein and Activity in Colorectal Cancer

Lonny G. M. Hazena, Fonnet E. Bleekera, Bjarne Lauritzenb, Sieglinde Bahnsb, Jiying Songa, Ard Jonkera, Bernard E. M. Van Driela, Hans Lyonc, Ulla Hansenc, Angela Köhlerb, and Cornelis J. F. Van Noordena
a Academic Medical Center, University of Amsterdam, Department of Cell Biology and Histology, Amsterdam, The Netherlands
b Department of Cell Biology and Pathology, Biologische Anstalt Helgoland in the Alfred Wegener Institute, Hamburg, Germany
c Københavns Kommunes Hvidovre Hospital, University of Copenhagen, Department of Pathology, Hvidovre, Denmark

Correspondence to: Cornelis J. F. Van Noorden, Dept. of Cell Biology and Histology, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. E-mail: c.j.vannoorden@amc.uva.nl

Cathepsin B is a lysosomal cysteine proteinase that may participate in cancer progression. We compared localization of its protein and activity during progression of human colorectal cancer. In adenomas and carcinomas, protein expression and, particularly, activity were elevated compared with those in normal colorectal mucosa. In normal mucosa, cathepsin B protein expression 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 adenomas and carcinomas contained moderate to high protein levels but little activity except for areas of angiogenesis, inflammation, and necrosis, in which activity was high. In adenomas and the majority of well-differentiated carcinomas and moderately differentiated carcinomas, cathepsin B protein and activity were found in granular form in the epithelium, close to the basement 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. Invasive fronts in most cancers contained moderate protein levels but high activity. We conclude that (a) activity localization is essential to understand the role of cathepsin B in cancer progression, and (b) cathepsin B activity in human colon is associated with invasion of cancer cells, endothelial cells, and inflammatory cells, and in cell death, both apoptotic and necrotic.

(J Histochem Cytochem 48:1421–1430, 2000)

Key Words: colorectal cancer, invasion, metastasis, cysteine proteinase, cathepsin B, immunohistochemistry, enzyme histochemistry, image analysis


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