Research article contains research data on the endogene inhibitor of cysteine cathepsins stefin B in transgenic mouse mammary cancer model. Lysosomal cysteine cathepsins contribute to proteolytic events promoting tumor growth and metastasis. Their enzymatic activity, however, is tightly regulated by endogenous inhibitors. To investigate the role of cathepsin inhibitor stefin B (StfB) in mammary cancer, StfB null mice were crossed with transgenic PyMT mammary cancer model mice. We show that ablation of StfB resulted in reduced size of mammary tumors but did not affect their rate of metastasis. Importantly, decrease in tumor growth was correlated with an increased incidence of dead cell islands detected in tumors of StfB-deficient mice. Ex vivo analysis of primary PyMT tumor cells revealed that upon treatment with the lysosomotropic agent Leu-Leu-OMe, cancer cells lacking StfB exhibited a higher sensitivity to apoptosis. Moreover, Stfb-ablated tumor cells were significantly more prone to cell death under increased oxidative stress. These results indicate an in vivo role for StfB in protecting cancer cells by promoting their resistance to oxidative stress and to apoptosis induced through the lysosomal pathway.
COBISS.SI-ID: 26964263