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

Wang, B ; Sun, J S ; Kitamoto, S ; Yang, M ; Grubb, Anders LU ; Chapman, H A ; Kalluri, R and Shi, G P (2006) In Journal of Biological Chemistry 281(9). p.6020-6029
Abstract
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... (More)
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. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
281
issue
9
pages
6020 - 6029
publisher
ASBMB
external identifiers
  • wos:000235568900083
  • pmid:16365041
  • scopus:33646827205
ISSN
1083-351X
DOI
10.1074/jbc.M509134200
language
English
LU publication?
yes
id
6d1797a1-f48f-4ba4-ba9b-9e39ef04d83f (old id 417130)
date added to LUP
2016-04-01 11:42:49
date last changed
2020-12-08 02:31:55
@article{6d1797a1-f48f-4ba4-ba9b-9e39ef04d83f,
  abstract     = {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.},
  author       = {Wang, B and Sun, J S and Kitamoto, S and Yang, M and Grubb, Anders and Chapman, H A and Kalluri, R and Shi, G P},
  issn         = {1083-351X},
  language     = {eng},
  number       = {9},
  pages        = {6020--6029},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Cathepsin S controls angiogenesis and tumor growth via matrix-derived angiogenic factors},
  url          = {http://dx.doi.org/10.1074/jbc.M509134200},
  doi          = {10.1074/jbc.M509134200},
  volume       = {281},
  year         = {2006},
}