Document Detail


Cathepsin S from both tumor and tumor-associated cells promote cancer growth and neovascularization.
MedLine Citation:
PMID:  23629809     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent murine studies have demonstrated that tumor-associated macrophages in the tumor microenvironment are a key source of the pro-tumorigenic cysteine protease, cathepsin S. We now show in a syngeneic colorectal carcinoma murine model that both tumor and tumor-associated cells contribute cathepsin S to promote neovascularization and tumor growth. Cathepsin S depleted and control colorectal MC38 tumor cell lines were propagated in both wild type C57Bl/6 and cathepsin S null mice to provide stratified depletion of the protease from either the tumor, tumor-associated host cells, or both. Parallel analysis of these conditions showed that deletion of cathepsin S inhibited tumor growth and development, and revealed a clear contribution of both tumor and tumor-associated cell derived cathepsin S. The most significant impact on tumor development was obtained when the protease was depleted from both sources. Further characterization revealed that the loss of cathepsin S led to impaired tumor vascularization, which was complemented by a reduction in proliferation and increased apoptosis, consistent with reduced tumor growth. Analysis of cell types showed that in addition to the tumor cells, tumor-associated macrophages and endothelial cells can produce cathepsin S within the microenvironment. Taken together, these findings clearly highlight a manner by which tumor-associated cells can positively contribute to developing tumors and highlight cathepsin S as a therapeutic target in cancer.
Authors:
Donna M Small; Roberta E Burden; Jakub Jaworski; Shauna M Hegarty; Shaun Spence; James F Burrows; Cheryl McFarlane; Adrien Kissenpfennig; Helen O McCarthy; James A Johnston; Brian Walker; Christopher J Scott
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-05-29
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  133     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-08-20     Completed Date:  2013-10-31     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2102-12     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 UICC.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Blotting, Western
Carcinoma, Lewis Lung / blood supply,  genetics,  pathology*
Cathepsins / physiology*
Cell Adhesion
Cell Cycle
Cell Movement*
Cell Proliferation*
Cells, Cultured
Colorectal Neoplasms / blood supply,  genetics,  pathology*
Endothelium, Vascular / cytology,  metabolism
Flow Cytometry
Fluorescent Antibody Technique
Humans
Immunoenzyme Techniques
Macrophages / cytology,  metabolism
Melanoma, Experimental / blood supply,  genetics,  pathology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Neovascularization, Pathologic*
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Tumor Microenvironment
Grant Support
ID/Acronym/Agency:
G0901615//Medical Research Council; //Medical Research Council
Chemical
Reg. No./Substance:
0/RNA, Messenger; EC 3.4.-/Cathepsins; EC 3.4.22.27/cathepsin S

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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