Document Detail


Ligation of TLR2 by versican: a link between inflammation and metastasis.
MedLine Citation:
PMID:  19608024     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Versican, a large extracellular matrix proteoglycan, accumulates both in tumor stroma and cancer cells. It participates in cell adhesion, migration, and angiogenesis, all features of invasion and metastasis. However, the mechanism(s) whereby versican promotes cancer invasion and metastasis is not yet fully understood. A recent study has documented that versican can activate tumor-infiltrating myeloid cells through toll-like receptor (TLR) 2 and its co-receptors TLR6 and CD14 and elicit the production of proinflammatory cytokines including TNF-alpha that enhance tumor metastasis. As both resident fibroblasts and endothelial cells (ECs) also express functional TLR2 and its co-receptors, we hypothesized that, in addition to myeloid cells, versican may trigger the activation of both fibroblasts and ECs. Of interest, TLR2-mediated activation of EC and fibroblast has been observed to increase the secretion of interleukin-8, a proinflammatory CXC chemokine that potentiates neutrophil infiltration and angiogenesis, as well as metastatic growth. Ligation of TLR2 by versican appears to be directly involved in the activation of multiple types of cells in tumor stroma and the induction of inflammatory cytokine secretion, providing a link between inflammation and cancer metastasis. Accordingly, antagonists of versican and TLR2 restrain the activation of tumor stromal cells, which may offer a novel approach to cancer therapy by targeting tumor microenvironment.
Authors:
Wei Wang; Ge-Liang Xu; Wei-Dong Jia; Jin-Liang Ma; Jian-Sheng Li; Yong-Sheng Ge; Wei-Hua Ren; Ji-Hai Yu; Wen-Bin Liu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-21
Journal Detail:
Title:  Archives of medical research     Volume:  40     ISSN:  1873-5487     ISO Abbreviation:  Arch. Med. Res.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-07-17     Completed Date:  2009-09-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9312706     Medline TA:  Arch Med Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  321-3     Citation Subset:  IM    
Affiliation:
Centre for the Study of Liver Cancer, Affiliated Provincial Hospital, Anhui Medical University, Hefei, China.
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MeSH Terms
Descriptor/Qualifier:
Cytokines / immunology,  metabolism*
Endothelial Cells / immunology,  metabolism
Extracellular Matrix / immunology,  metabolism
Fibroblasts / immunology,  metabolism
Humans
Inflammation / immunology*,  metabolism
Neoplasm Metastasis
Neoplasms / pathology*
Toll-Like Receptor 2 / immunology,  metabolism*
Versicans / immunology,  metabolism*
Chemical
Reg. No./Substance:
0/Cytokines; 0/Toll-Like Receptor 2; 126968-45-4/Versicans

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


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