CHARACTERIZATION OF CYSTEINE PROTEASES AND THEIR ENDOGENOUS INHIBITORS IN MCF-7 AND ADRIAMYCIN-RESISTANT MCF-7 HUMAN BREAST-CANCER CELLS

The expression of three lysosomal cysteine proteases was examined in a lowly metastatic, MCF-7 human breast cancer cell line and its highly metastatic, Adriamycin-resistant variant, MCF-7/Adr(R). While levels of cathepsin H activity were similar in all cell lines at each stage of growth, intracellular cathepsin B and L activities were highest in MCF-7/Adr(R). These high levels were accompanied by growth-related increases in acid/pepsin-activatable cathepsin activity in the culture medium. Analyses of endogenous cathepsin B inhibitor activity in control and heat-treated cell homogenates after fractionation by fast protein liquid chromatography suggested that alterations in cystatin-like, cysteine protease inhibitor activities contribute to increased levels of cathepsin activities in metastatic MCF-7/Adr(R) cells.