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Int. J. Mol. Sci. 2017, 18(1), 22; doi:10.3390/ijms18010022

Tumor-Derived Tissue Factor Aberrantly Activates Complement and Facilitates Lung Tumor Progression via Recruitment of Myeloid-Derived Suppressor Cells

1
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1
,
2
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2,* and 1,3,*
1
Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China
2
Department of Pathogenic Biology, Third Military Medical University, Chongqing 400037, China
3
Chongqing Key Laboratory of Tumor Immunotherapy, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Li Yang
Received: 14 November 2016 / Revised: 9 December 2016 / Accepted: 15 December 2016 / Published: 19 January 2017
(This article belongs to the Special Issue Tumor Microenvironment and Metabolism)
View Full-Text   |   Download PDF [5290 KB, uploaded 19 January 2017]   |  

Abstract

The initiator of extrinsic coagulation, tissue factor (TF), and its non-coagulant isoform alternatively spliced TF (asTF) are closely associated with tumor development. In the tumor microenvironment, the role of TF-induced coagulation in tumor progression remains to be fully elucidated. Using TF-knockdown lung tumor cells, we showed that TF is the dominant component of procoagulant activity but is dispensable in the cellular biology of tumor cells. In a xenograft model, using immunohistochemical analysis and flow cytometry analysis of the tumor microenvironment, we demonstrated that TF-induced fibrin deposition, which is correlated with complement activation and myeloid-derived suppressor cell (MDSC) recruitment, is positively associated with tumor progression. C5aR antagonism blunted the effect of TF on tumor progression and decreased MDSC recruitment. In conclusion, our data suggested that in tumor microenvironment, TF-induced coagulation activated the complement system and subsequently recruited myeloid-derived suppressor cells to promote tumor growth, which brings new insights into the coagulation-induced complement activation within the tumor microenvironment during tumor progression. View Full-Text
Keywords: tumor-derived tissue factor; complement; myeloid-derived suppressor cells tumor-derived tissue factor; complement; myeloid-derived suppressor cells
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Han, X.; Zha, H.; Yang, F.; Guo, B.; Zhu, B. Tumor-Derived Tissue Factor Aberrantly Activates Complement and Facilitates Lung Tumor Progression via Recruitment of Myeloid-Derived Suppressor Cells. Int. J. Mol. Sci. 2017, 18, 22.

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