Wang, BingSun, JiusongKitamoto, ShiroYang, MinGrubb, AndersChapman, Harold A.Kalluri, RaghuShi, Guo-Ping2019-10-142006Wang, Bing, Jiusong Sun, Shiro Kitamoto, Min Yang, Anders Grubb, Harold A. Chapman, Raghu Kalluri, and Guo-Ping Shi. 2006. “Cathepsin S Controls Angiogenesis and Tumor Growth via Matrix-Derived Angiogenic Factors.” Journal of Biological Chemistry 281 (9): 6020–29. doi:10.1074/jbc.M509134200.0021-92581083-351Xhttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41543160The cysteine protease cathepsin S is highly expressed in malignant tissues. By using a mouse model of multistage murine pancreatic islet cell carcinogenesis in which cysteine cathepsin activity has been functionally implicated, we demonstrated that selective cathepsin S deficiency impaired angiogenesis and tumor cell proliferation, thereby impairing angiogenic islet formation and the growth of solid tumors, whereas the absence of its endogenous inhibitor cystatin C resulted in opposite phenotypes. Although mitogenic vascular endothelial growth factor, transforming growth factor-beta 1, and the anti-angiogenic endostatin levels in either serum or carcinoma tissue extracts did not change in cathepsin S- or cystatin C-null mice, tumor tissue basic fibroblast growth factor and serum type 1 insulin growth factor levels were higher in cystatin C-null mice, and serum type 1 insulin growth factor levels were also increased in cathepsin S-null mice. Furthermore, cathepsin S affected the production of type IV collagen-derived anti-angiogenic peptides and the generation of bioactive pro-angiogenic gamma 2 fragments from laminin-5, revealing a functional role for cathepsin S in angiogenesis and neoplastic progression.en-USJournal Article2019-10-1410.1074/jbc.M509134200