title: Tumor-Derived Tissue Factor Aberrantly Activates Complement and Facilitates Lung Tumor Progression via Recruitment of Myeloid-Derived Suppressor Cells.
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.
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. hanx310@tmmu.edu.cn.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. zhahaoran@tmmu.edu.cn.
authors.forename: Haoran
authors.initials: H
authors.lastname: Zha
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing 400037, China. yangf129@tmmu.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing 400037, China. guobo@tmmu.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Guo
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. bo.zhu@tmmu.edu.cn.|Chongqing Key Laboratory of Tumor Immunotherapy, Xinqiao Hospital, Third Military Medical University, Chongqing 400038, China. bo.zhu@tmmu.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhu
mesh_terms: D000072283:A549 Cells; D000818:Animals; D017209:Apoptosis; D001777:Blood Coagulation; D049109:Cell Proliferation; D003167:Complement Activation; D018450:Disease Progression; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology*; D008819:Mice, Nude; D000072737:Myeloid-Derived Suppressor Cells / Q000378:metabolism*; D044087:Receptor, Anaphylatoxin C5a / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D044087:Receptor, Anaphylatoxin C5a; D013925:Thromboplastin
keywords: complement; myeloid-derived suppressor cells; tumor-derived tissue factor