Document Detail

Endothelial cell-expressed Tim-3 facilitates metastasis of melanoma cells by activating the NF-kappaB pathway.
MedLine Citation:
PMID:  20664975     Owner:  NLM     Status:  MEDLINE    
T cell immunoglobulin and mucin domain-3 (Tim-3) is originally recognized as a receptor of Th1 cells. We found that Tim-3 could be expressed in endothelial cells after stimulation with tumor cell-released TLR4 ligand. Tim-3 expressed by endothelial cells does not function as the receptor of galectin-9, but mediates the interaction of endothelial cells with tumor cells. The engagement of endothelial cell-expressed Tim-3 with a non-galectin 9 putative receptor on B16 melanoma cells could trigger the NF-kappaB signaling pathway in B16 cells. The activated NF-kappaB not only promoted the proliferation of B16 cells, but also enhanced apoptosis resistance of B16 cells by up-regulating Bcl-2 and Bcl-xL and down-regulating Bax. Consistently, Tim-3 facilitated the survival of B16 cells in the blood stream, arrested in the lung and following invasion, resulted in more metastatic nodules in the lung. These findings suggest that endothelial cell-expressed Tim-3 increases tumor cell metastatic potential by facilitating tumor cell intravasation, survival in blood stream and extravasation. Thus, anti-inflammation or blockade of Tim-3 may contribute to the prevention of metastasis.
Feng-Hua Wu; Ye Yuan; Dong Li; Zhang Lei; Chuan-Wang Song; Yan-Yan Liu; Bo Li; Bo Huang; Zuo-Hua Feng; Gui-Mei Zhang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncology reports     Volume:  24     ISSN:  1791-2431     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-07-28     Completed Date:  2010-11-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  693-9     Citation Subset:  IM    
Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
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MeSH Terms
CHO Cells
Cell Proliferation
Cell Survival
Endothelial Cells / metabolism*
HMGB1 Protein / metabolism
Lung Neoplasms / genetics,  metabolism*,  pathology
Melanoma, Experimental / blood supply,  genetics,  metabolism*,  pathology
Mice, Inbred C57BL
NF-kappa B / metabolism*
Neoplasm Invasiveness
Paracrine Communication
Proto-Oncogene Proteins c-bcl-2 / metabolism
Receptors, Virus / genetics,  metabolism*
Time Factors
Toll-Like Receptor 4
bcl-2-Associated X Protein / metabolism
bcl-X Protein / metabolism
Reg. No./Substance:
0/Bax protein, mouse; 0/Bcl2l1 protein, mouse; 0/HMGB1 Protein; 0/Havcr2 protein, mouse; 0/Ligands; 0/NF-kappa B; 0/Proto-Oncogene Proteins c-bcl-2; 0/Receptors, Virus; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 4; 0/bcl-2-Associated X Protein; 0/bcl-X Protein

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