Malignancy cathepsins

PI. Pagano, M., Dalet-Fumeron, V., and Engler, R., The glycosylation state of the precursors of the cathepsin-iike proteinase from human malignant ascitic fluid Possible implication in the secretory pathways of these proenzymes. Cancer Lett. 45, 13-19 (1989). 

Sloane BF, Moin K, Krepela E, Rhozhin J (1990) Cathepsin B and its endogenous inhibitors the role in tumor malignancy. Cancer Metastasis Rev 9 333-352... 

Crocker J, Burnett D, Jones EL. Immunohistochemical demonstration of cathepsin B in the macrophages of benign and malignant lymphoid tissues./ Pathol. 1984 142 87-94. 

Several lines of evidence indicate that neoplastic cells per se are the main source of extracellular thiol proteinase activity. Recent studies (39) have shown that malignant human breast tumors maintained in organ culture secrete high levels of a cathepsin B-like enzyme into the culture medium. Moreover high levels of cathepsin B-like enzyme are present in the serum of patients with a wide variety of cancers, and these levels decrease when the cancer tissue is removed or treated with therapeutic agents (64, 65). Cathepsin B-like enzyme from cultured cells of malignant tumors (39,66) possesses enzymic properties similar to those of cathepsin B with respect to specificity, affinity, and pH optima for synthetic substrates. It hydrolyzes Bz-Arg-Arg-2-naphthylamide and is inhibited by leupeptin. However, the tumor enzyme is much more stable than cathepsin B to inactivation above pH 7. It has a molecular weight of about 33,000-35,000. The distribution of cathepsin B-like activity was determined in fractions of control and neoplastic epithelial cells from human ectocervix (66). The activity is present mainly in the mitochondrial and lysosomal fractions of normal cells but mainly in the plasma membranes and nuclei of neoplastic cells. 

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