Deletion of cathepsin H perturbs angiogenic switching, vascularization and growth of tumors in a mouse model of pancreatic islet cell cancer Journal Article

   

Authors:	Gocheva, V.; Chen, X.; Peters, C.; Reinheckel, T.; Joyce, J. A.
Article Title:	Deletion of cathepsin H perturbs angiogenic switching, vascularization and growth of tumors in a mouse model of pancreatic islet cell cancer
Abstract:	Proteases can regulate many aspects of tumor development as their actions, which include degradation of the extracellular matrix, proteolytic processing of chemokines and activation of other enzymes, influence several key tumorigenic processes. Members of one protease class, the cysteine cathepsins, have received increasing recognition for their involvement in cancer development, and numerous clinical studies have reported correlations between elevated cathepsin levels and malignant progression. This is also the case for cathepsin H, a member of the cysteine cathepsin family, and its utility as a prognostic marker has been analyzed extensively. However, there is limited information available on its specific functions in tumor development and progression. To gain further insight into the role of this protease in cancer, we crossed cathepsin H-deficient mice with the RIP1-Tag2 model of pancreatic islet carcinogenesis. Deletion of cathepsin H significantly impaired angiogenic switching of the premalignant hyperplastic islets and resulted in a reduction in the subsequent number of tumors that formed. Moreover, the tumor burden in cathepsin H null RT2 mice was significantly reduced, in association with defects in the blood vasculature and increased apoptosis. Thus, we demonstrate here for the first time important tumor-promoting roles for cathepsin H in vivo using a mouse model of human cancer. Copyright © by Walter de Gruyter.
Keywords:	immunohistochemistry; protein expression; gene deletion; nonhuman; conference paper; pancreatic neoplasms; mouse; animals; mice; animal tissue; gene targeting; mus; apoptosis; tumor volume; clinical assessment; animal experiment; animal model; in vivo study; angiogenesis; neovascularization, pathologic; mice, inbred c57bl; carcinogenesis; transgenic mouse; mice, transgenic; cancer invasion; tumor burden; disease progression; gtpase-activating proteins; tumor growth; gene switching; tumor vascularization; cd31 antigen; insulinoma; pancreas islet cell carcinoma; mouse model; protease; cathepsin h; pancreatic endocrine cancer
Journal Title:	Biological Chemistry
Volume:	391
Issue:	8
ISSN:	1431-6730
Publisher:	Walter de Gruyter GmbH
Date Published:	2010-08-01
Start Page:	937
End Page:	945
Language:	English
DOI:	10.1515/bc.2010.080
PUBMED:	20731543
PROVIDER:	scopus
PMCID:	PMC3126667
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-77955964441&partnerID=40&md5=bfd241c7c4973b889b5adba7d039d022
Notes:	--- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: BICHF" - "Source: Scopus"

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