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Immunohistochemical and Biochemical Study of a Cathepsin B-like Proteinase in Human Colonic Cancers¹

Biochemistry Laboratory, U. E. R. Broussais-Hôtel Dieu, 15 rue de l'Ecole de Médecine, 75270 Paris Cedex 06 [D. K., V. D-F., M. P.]; and the Immunochemistry Laboratory (ER 277 CNRS), Institut de Recherches Scientifiques sur le Cancer, B.P. 8, 94802 Villejuif Cedex; France [M. C. F., P. B.]

An immunohistological study was carried out on 51 human colorectal adenocarcinomas and eight samples of histologically normal colonic mucosa removed far from tumors, using anti-rabbit cathepsin B and anti-human cathepsin B immunoglobulins. Positive reactions were obtained on tumor cells and macrophage-like cells. However, as these immunoglobulins could not discriminate between cathepsin B and cathepsin B-like proteinases, and as they cross-reacted with cathepsins H and L, a partial characterization of the proteinase activities was performed in order to identify the type of enzyme present in the positive cells.

The levels of cathepsins H and L were very low in extracts of colorectal tumors and normal colonic mucosa. A peculiar cathepsin B-like proteinase activity with pH optimum at 6.8 was found in tumor extracts together with the lysosomal cathepsin B, whereas normal colonic mucosa showed only cathepsin B activity (pH optimum, 6.0). These results indicate that lysosomal cathepsin B is responsible for staining of macrophage-like cells found in the lamina propria of colonic mucosa and in the peritumoral stroma. Immunohistochemical staining of colonic tumor cells observed in 29/51 cases seems on the other hand to be primarily due to a cathepsin B-like proteinase.

Three colonic tumor cell lines, Colo-205, HT-29, and SW-1116, were also studied using the same methods. These cells produced a latent cathepsin B-like proteinase which, after activation, was similar to that found in tumor extracts. This latent proteinase was detected mainly in the culture media. The cultured colonic tumor cells, after staining by anti-cathepsin B antibodies, showed strongly positive granules.

In conclusion, this work demonstrates that malignant colonic cells are the source of a cathepsin B-like proteinase, with optimal activity near neutrality. Its secretion into the extracellular space indicates furthermore, that it may be an important component of the "proteinase cascade" associated with tumor invasion and metastasis.

¹ This work was supported in part by grants from the Association pour la Recherche sur le Cancer (ARC), Villejuif and from the Université Pierre et Marie Curie, Paris.

² Recipient of an ARC-fellowship.

³ To whom requests for reprints should be addressed.

Received 3/23/88. Revised 8/10/88. Accepted 9/ 6/88.

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