Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein

Le-Xing Yu, Lei Yan, Wen Yang, Fu-Quan Wu, Yan Ling, Shu-Zhen Chen, Liang Tang, Ye-Xiong Tan, Dan Cao, Meng-Chao Wu, He-Xin Yan () and Hong-Yang Wang ()
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Le-Xing Yu: National Center for Liver Cancer, Second Military Medical University
Lei Yan: National Center for Liver Cancer, Second Military Medical University
Wen Yang: National Center for Liver Cancer, Second Military Medical University
Fu-Quan Wu: National Center for Liver Cancer, Second Military Medical University
Yan Ling: National Center for Liver Cancer, Second Military Medical University
Shu-Zhen Chen: National Center for Liver Cancer, Second Military Medical University
Liang Tang: National Center for Liver Cancer, Second Military Medical University
Ye-Xiong Tan: National Center for Liver Cancer, Second Military Medical University
Dan Cao: National Center for Liver Cancer, Second Military Medical University
Meng-Chao Wu: National Center for Liver Cancer, Second Military Medical University
He-Xin Yan: National Center for Liver Cancer, Second Military Medical University
Hong-Yang Wang: National Center for Liver Cancer, Second Military Medical University

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: Abstract Increasing evidence suggests that TLR4 expression by tumour cells promotes tumour progression, but it is unclear whether TLR4 is involved in metastasis. Here we show that TLR4 deficiency significantly diminishes experimental lung metastasis without affecting primary tumour growth. Bone marrow transplantation experiment and application of antiplatelet agents in mice demonstrate that TLR4 on platelets plays an important role in metastasis. TLR4 is critical for platelet–tumour cell interaction in vitro. Furthermore, high-mobility group box1 (HMGB1) neutralization attenuates platelet–tumour cell interaction in vitro and metastasis in vivo in a TLR4-dependent manner, indicating that tumour cell-released HMGB1 is the key factor that interacts with TLR4 on platelets and mediates platelet–tumour cell interaction, which promotes metastasis. These findings demonstrate a mechanism by which platelets promote tumour cell metastasis and suggest TLR4, and its endogenous ligand HMGB1 as targets for antimetastatic therapies.

Date: 2014
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DOI: 10.1038/ncomms6256

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