FGL2/凝血酶原酶下调可延迟HCCLM6异种移植物肿瘤生长和减少肿瘤血管生成

Downregulation of FGL2/prothrombinase delays HCCLM6 xenograft tumour growth and decreases tumour angiogenesis
作者:Liu, Y.a, Xu, L.a, Zeng, Q.a, Wang, J.a, Wang, M.a
机构: 华中科技大学同济医学院附属同济医院感染科 感染性疾病研究所
期刊: LIVER INT2012年10月10期32卷

Background: Fibrinogen-like protein 2 (FGL2), which directly generates thrombin from prothrombin without activation of the conventional coagulation cascade, was shown to be overexpressed in various human malignant tumours. Aims: Herein, we aimed to investigate its expression pattern, biological function and mechanism of action in hepatocellular carcinoma (HCC). Methods: FGL2 expression and colocalization with fibrin was examined in 15 HCC tissues. FGL2 downregulation was performed by targeting microRNA in a HCCLM6 cell line in which FGL2 was highly expressed in xenografts of nude mice. The effects of FGL2 knockdown on tumour growth and angiogenesis were evaluated in vitro and in vivo. Cytometric bead arrays were employed to identify FGL2-regulated signalling pathways. Results: FGL2 was overexpressed in HCC tissues and colocalized with fibrin deposition. Knockdown of FGL2 expression in HCCLM6 cells (hFGL2 low HCCLM6) resulted in delayed xenografts tumour growth within an observation period of 42 days and decreased vascularization, which was accompanied by decreased phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). In vitro hFGL2 low HCCLM6 cells exhibited decreased proliferation without significant induction of apoptosis. Overexpression of FGL2 in HCCLM6 cells or addition of recombinant hFGL2 protein induced phosphorylation of p38-MAPK and ERK1/2 involving protease-activated receptors (PARs).activation. Conclusions: FGL2 contributes to HCC tumour growth and angiogenesis in a thrombin-dependent manner, and downregulation of its expression might be of therapeutic significance in HCC. © 2012 John Wiley & Sons A/S.

Department and Institute of Infectious Disease, Tongji hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

通讯作者:Ning, Q.; Department and Institute of Infectious Disease, Tongji hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; email:qning66@yahoo.com.cn
学科代码:消化病学   关键词:肿瘤血管生成
来源: Scopus
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