|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|
|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|
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
|项目编号||30872469 ; 30801092|
|资助机构||National Natural Science Foundation of China ; National Natural Science Youth Foundation of China|
|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
|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.|