Han Xiao, Zha Haoran, Yang Fei, Guo Bo, Zhu Bo
Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Department of Pathogenic Biology, Third Military Medical University, Chongqing 400037, China.
Int J Mol Sci. 2017 Jan 19;18(1):22. doi: 10.3390/ijms18010022.
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.
外源性凝血的启动因子组织因子（TF）及其非凝血性异构体可变剪接组织因子（asTF）与肿瘤发展密切相关。在肿瘤微环境中，TF诱导的凝血在肿瘤进展中的作用仍有待充分阐明。利用TF敲低的肺癌细胞，我们发现TF是促凝活性的主要成分，但在肿瘤细胞的细胞生物学中并非必需。在异种移植模型中，通过对肿瘤微环境进行免疫组织化学分析和流式细胞术分析，我们证明TF诱导的纤维蛋白沉积与补体激活和髓源性抑制细胞（MDSC）募集相关，与肿瘤进展呈正相关。C5aR拮抗作用减弱了TF对肿瘤进展的影响，并减少了MDSC募集。总之，我们的数据表明，在肿瘤微环境中，TF诱导的凝血激活补体系统，随后募集髓源性抑制细胞以促进肿瘤生长，这为肿瘤进展过程中肿瘤微环境内凝血诱导的补体激活带来了新的见解。
