Ligation of TLR2 by versican: a link between inflammation and metastasis.
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.
Wang
Wei
W
Centre for the Study of Liver Cancer, Affiliated Provincial Hospital, Anhui Medical University, Hefei, China.
Xu
Ge-Liang
GL
Jia
Wei-Dong
WD
Ma
Jin-Liang
JL
Li
Jian-Sheng
JS
Ge
Yong-Sheng
YS
Ren
Wei-Hua
WH
Yu
Ji-Hai
JH
Liu
Wen-Bin
WB
D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology*; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism*; D053675:Versicans / Q000276:immunology / Q000378:metabolism*
D016207:Cytokines; D051195:Toll-Like Receptor 2; D053675:Versicans