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Extrahepatic synthesis of coagulation factor VII by colorectal cancer cells promotes tumor invasion and metastasis
Tang Jian-qiang1; Fan Qing2; Wu Wen-han1; Jia Zhi-chao1; Li Hui1; Yang Yin-mo1; Liu Yu-cun1; Wan Yuan-lian1
关键词colorectal neoplasms thromboplastin blood coagulation factors neoplasm metastasis matrix metalloproteinases
刊名CHINESE MEDICAL JOURNAL
2010-12-20
DOI10.3760/cma.j.issn.0366-6999.2010.24.011
123期:24页:3559-3565
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, General & Internal
研究领域[WOS]General & Internal Medicine
关键词[WOS]TISSUE FACTOR EXPRESSION ; BLOOD-COAGULATION ; GROWTH-FACTOR ; IN-VITRO ; ANGIOGENESIS ; ACTIVATION ; CARCINOMA ; MIGRATION ; RECEPTOR ; COMPLEX
英文摘要

Background Blood coagulation factor VII (FVII) is physiologically synthesized in the liver and released into the blood. Binding of FVII to tissue factor (TF) is related to the metastatic potential of tumor cells, also a significant risk factor in the development of hepatic metastasis in patients with colorectal cancer (CRC). It has been found that some cancer cells can produce FVII extrahepatically. However, little is known about FVII and CRC. We therefore hypothesized that CRC cells may synthese FVII, leading to tumor invasion and metastasis.

Methods We detected the expression of FVII protein in 55 CRC specimens by immunohistochemical staining. The FVII mRNA in 45 of 55 CRC cases, 6 colon cancer cell lines and one hepatoma cell line was measured by real-time reverse transcription-PCR (RT-PCR). Transwell invasion assays were performed to evaluate the changes of cell migration and invasion of LoVo cancer cells in vitro. We further observed the likely effectors regulated by the TF/FVIIa complex Western blotting assay.

Results Extrahepatic synthesis of FVII was detected in the cytoplasm of 32 (58.2%) CRC specimens by immunohistochemistry, but not in normal mucosa. Liver metastasis (P=0.003) and TNM staging (P=0.005) were significantly correlated with FVII antigen expression. The positive ratios in stages I, II, III and IV were 33.3%, 40.0%, 52.4% and 87.5%, respectively. The expression of FVII mRNA in CRC with hepatic metastasis was significantly higher than CRC without hepatic metastasis (5.33 +/- 2.88 vs. 1.47 +/- 0.51, P=0.03). Ectopic FVIIa induced a slight increase (1.34-fold) in the number of migrating cells, which was inhibited by the specific TF antibody. The formation of TF/FVIIa complex resulted in a marked increase in the expression of matrix metalloproteinases (MMP)-2 (3.5-fold) and MMP-9 (4.7-fold) in a time-dependent and dose-dependent manner.

Conclusions Extrahepatic synthesis of FVII by CRC cells may promote tumor invasion and metastasis. MMPs, as downstream effectors of TF/FVIIa signaling, facilitate the development of metastasis in colon cancer. Chin Med J 2010;123(24):3559-3565

语种英语
WOS记录号WOS:000285799200011
项目编号30872469 ; 30801092
资助机构National Natural Science Foundation of China ; National Natural Science Youth Foundation of China
引用统计
被引频次:2[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58717
专题北京大学第一临床医学院_普通外科
作者单位1.Beijing Shijitan Hosp, Dept Gen Surg, Beijing 100034, Peoples R China
2.Peking Univ First Hosp, Dept Gen Surg, Beijing 100034, Peoples R China
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Tang Jian-qiang,Fan Qing,Wu Wen-han,et al. Extrahepatic synthesis of coagulation factor VII by colorectal cancer cells promotes tumor invasion and metastasis[J]. CHINESE MEDICAL JOURNAL,2010,123(24):3559-3565.
APA Tang Jian-qiang.,Fan Qing.,Wu Wen-han.,Jia Zhi-chao.,Li Hui.,...&Wan Yuan-lian.(2010).Extrahepatic synthesis of coagulation factor VII by colorectal cancer cells promotes tumor invasion and metastasis.CHINESE MEDICAL JOURNAL,123(24),3559-3565.
MLA Tang Jian-qiang,et al."Extrahepatic synthesis of coagulation factor VII by colorectal cancer cells promotes tumor invasion and metastasis".CHINESE MEDICAL JOURNAL 123.24(2010):3559-3565.
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