Liver Cancer
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Oct 21, 2008; 14(39): 5980-5989
Published online Oct 21, 2008. doi: 10.3748/wjg.14.5980
Fibrinogen-like protein 2/fibroleukin prothrombinase contributes to tumor hypercoagulability via IL-2 and IFN-γ
Kai Su, Fang Chen, Wei-Ming Yan, Qi-Li Zeng, Li Xu, Dong Xi, Bin Pi, Xiao-Ping Luo, Qin Ning
Kai Su, Fang Chen, Wei-Ming Yan, Qi-Li Zeng, Li Xu, Dong Xi, Bin Pi, Xiao-Ping Luo, Qin Ning, Department of Infectious Diseases and Pediatrics, Institute of Infectious Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, Hubei Province, China
Author contributions: Su K, Chen F, Luo XP and Ning Q designed the research; Su K, Chen F, Yan WM, Zeng QL, Xu L, Xi D and Pi B performed the research; Su K and Chen F analyzed data; and Su K, Luo XP and Ning Q wrote the paper.
Supported by The Natural Science Foundation of China, NSFC (30672380, 30571643); National Key Basic Research Program of China (2007CB512900, 2005CB522901, 2005CB522507) and 11th Five-Year Plan Key Project (2006BAI05A07)
Correspondence to: Qin Ning, MD, PhD, Department of Infectious Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, Hubei Province, China. qning@tjh.tjmu.edu.cn
Telephone: +86-27-83662391 Fax: +86-27-83662391
Received: April 22, 2008
Revised: September 12, 2008
Accepted: September 17, 2008
Published online: October 21, 2008
Abstract

AIM: To examine the role of Fibrinogen-like protein 2 (fgl2)/fibroleukin in tumor development. Fgl2 has been reported to play a vital role in the pathogenesis in MHV-3 (mouse hepatitis virus) induced fulminant and severe hepatitis, spontaneous abortion, allo- and xeno- graft rejection by mediating “immune coagulation”.

METHODS: Tumor tissues from 133 patients with six types of distinct cancers and the animal tumor tissues from human hepatocellular carcinoma (HCC) model on nude mice (established from high metastasis HCC cell line MHCC97LM6) were obtained.

RESULTS: Hfgl2 was detected in tumor tissues from 127 out of 133 patients as well as tumor tissues collected from human HCC nude mice. Hfgl2 was highly expressed both in cancer cells and interstitial inflammatory cells including macrophages, NK cells, and CD8+ T lymphocytes and vascular endothelial cells. Hfgl2 mRNA was localized in cells that expressed hfgl2 protein. Fibrin (nogen) co-localization with hfgl2 expression was determined by dual immunohistochemical staining. In vitro, IL-2 and IFN-γ increased hfgl2 mRNA by 10-100 folds and protein expression in both THP-1 and HUVEC cell lines. One-stage clotting assays demonstrated that THP-1 and HUVEC cells expressing hfgl2 had increased procoagulant activity following cytokines stimulation.

CONCLUSION: The hfg12 contributes to the hypercoagulability in cancer and may induce tumor angiogenesis and metastasis via cytokine induction.

Keywords: Fibrinogen-like protein 2/fibroleukin; Thrombin; Tumor; Coagulation; Cytokine