| First Author | Wang B | Year | 2006 |
| Journal | J Biol Chem | Volume | 281 |
| Issue | 9 | Pages | 6020-9 |
| PubMed ID | 16365041 | Mgi Jnum | J:109218 |
| Mgi Id | MGI:3626130 | Doi | 10.1074/jbc.M509134200 |
| Citation | Wang B, et al. (2006) Cathepsin S controls angiogenesis and tumor growth via matrix-derived angiogenic factors. J Biol Chem 281(9):6020-9 |
| abstractText | The 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-beta1, 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 gamma2 fragments from laminin-5, revealing a functional role for cathepsin S in angiogenesis and neoplastic progression. |
