期刊
EUROPEAN JOURNAL OF CANCER
卷 47, 期 14, 页码 2230-2239出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2011.04.028
关键词
Pancreatic cancer; Tissue factor; Metastasis; Blood coagulation; Matrix metalloproteinase 9
类别
资金
- Ministry of Health, Labor and Welfare (Matsumura) [H19-025]
- Ministry of Education, Culture, Sports, Science and Technology (Matsumura) [17016087]
- Japanese Foundation for Multidisciplinary Treatment of Cancer (Matsumura)
- Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program)
- Princess Takamatsu Cancer Research Fund [07-23908]
- Japan Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [17016087] Funding Source: KAKEN
Tissue factor (TF), the initiating cell surface receptor for the blood coagulation cascade, plays an important role in malignant transformation of the pancreas, although the precise mechanism remains unresolved. Here, we report that the TF - factor Vila complex in human pancreatic cancer cells produced a significant amount of MMP-9 and promoted invasion ability in vitro and invasion and metastasis in vivo. For treatment, we successfully developed an anti-human TF monoclonal antibody that inhibits both cellular signalling and blood coagulation cascade via TF. Invasive capability and MMP-9 expression were significantly reduced by the antibody. The antibody inhibited not only tumour invasion in the orthotopic model, but also haematogenous metastasis in the portal-injection liver metastasis model. In conclusion, the TF-VIIa complex plays an important role in invasion-metastasis by enhancing tumour cell infiltration ability and forming microthrombi. The newly established anti-human TF neutralisation antibody may be useful for the treatment of pancreatic and other invasive cancers. (C) 2011 Elsevier Ltd. All rights reserved.
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