Review article contains data on cysteine cathepsin and their involvment in different pathological conditions and their potential as prognosti and diagnostic biomarkers. It was discovered that proteolytic activity of cysteine cathepsin play important role in several pathological processes such as cancer, arthritis and atherosceloris. Most importantly their localization was found not only to be limited to the lysosomes but were present also in the extracellular mileu. In the light of those findings, it is not surprising that cysteine cathepsins are currently considered as highly relevant clinical targets.
COBISS.SI-ID: 27525671
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
Review articles contains data on cysteine cathepsins and their extracellular functions linked with ECM degradation, including regulation of their activity, which is often enhanced by acidification of the extracellular microenvironment, such as found in the bone resorption lacunae or tumor microenvironment. There are severeal substrates of cysteine cathepsins in ECM such as collagen and elastin that play important role in pathologies. Therefore cysteine cathepsin presents them self as a promissing target for therapies, since they are among the major proteases involved in ECM remodeling, and their role is not limited only to degradation. Deregulation of their activity is linked with numerous ECM-linked diseases and they are now validated targets in a number of them. Cathepsins S and K are themost attractive targets, especially cathepsin K as a major therapeutic target for osteoporosis with drugs targeting it in advanced clinical trials.
COBISS.SI-ID: 27616039
Reviw article contains analysis of different mouse cancer model and impact of cysteine cathepsins on tumor progression. By crossing various types of mouse cancer models with mice where specific cathepsins have been ablated, we contributed to this gap of knowledge and will summarize the results in this report. The employed models are the Rip1-Tag2 model for pancreatic neuroendocrine tumors, the K14-HPV16 model for squamous skin and cervical cancers, and the MMTV-PyMT model for metastasizing breast cancer, the KPC model for pancreatic ductal adenocarcinoma, and the APCmin mice developing early stages of intestinal neoplasia. In all these models deletion of cathepsin B led to suppression of the aggressiveness of the respective cancer pheno-type. However for some cathpesins it was revealed that they have different roles in different cancer models from progression to regression. A logical consequence of these results would be to further pursue selective inhibition of cathepsin B.
COBISS.SI-ID: 25963815