Journal
BIOLOGICAL CHEMISTRY
Volume 397, Issue 9, Pages 871-881Publisher
WALTER DE GRUYTER GMBH
DOI: 10.1515/hsz-2016-0138
Keywords
aspartyl protease; cathepsins; pericellular proteolysis; substrate specificity; tumor microenvironment; zymogen
Categories
Funding
- NCI NIH HHS [R21 CA186077, P41 CA196276, R21 CA185689] Funding Source: Medline
- NIGMS NIH HHS [T32 GM008155, T32 GM007175] Funding Source: Medline
Ask authors/readers for more resources
The cathepsin family of lysosomal proteases is increasingly being recognized for their altered expression in cancer and role in facilitating tumor progression. The aspartyl protease cathepsin E is overexpressed in several cancers and has been investigated as a biomarker for pancreatic ductal adenocarcinoma (PDAC). Here we show that cathepsin E expression in mouse PDAC tumors is increased by more than 400-fold when compared to healthy pancreatic tissue. Cathepsin E accumulates over the course of disease progression and accounts for more than 3% of the tumor protein in mice with end-stage disease. Through immunoblot analysis we determined that only -procathepsin E exists in mouse PDAC tumors and cell lines derived from these tumors. By decreasing the pH, this procathepsion E is converted to the mature form, resulting in an increase in proteolytic activity. Although active site inhibitors can bind procathepsin E, treatment of PDAC mice with the aspartyl protease inhibitor ritonavir did not decrease tumor burden. Lastly, we used multiplex substrate profiling by mass spectrometry to identify two synthetic peptides that are hydrolyzed by procathepsin E near neutral pH. This work represents a comprehensive analysis of procathepsin E in PDAC and could facilitate the development of improved biomarkers for disease detection.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available