Cathepsin S controls angiogenesis and tumor growth via matrix-derived angiogenic factors

Summary, in English

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-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.

• Författare: B Wang; J S Sun; S Kitamoto; M Yang; Anders Grubb; H A Chapman; R Kalluri; G P Shi
• Avdelning/ar: Avdelningen för klinisk kemi och farmakologi
• Publiceringsår: 2006
• Språk: Engelska
• Sidor: 6020-6029
• Publikation/Tidskrift/Serie: Journal of Biological Chemistry
• Volym: 281
• Issue: 9
• Länkar: http://dx.doi.org/10.1074/jbc.M509134200
• Dokumenttyp: Artikel i tidskrift
• Förlag: American Society for Biochemistry and Molecular Biology
• Ämne: Medicinal Chemistry; Pharmacology and Toxicology
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 1083-351X