Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, and Laboratory of Cancer Biology, Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan.
Eur J Cancer. 2011 Sep;47(14):2230-9. doi: 10.1016/j.ejca.2011.04.028. Epub 2011 May 27.
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 VIIa 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.
组织因子（TF）是血液凝血级联反应的起始细胞表面受体，在胰腺恶性转化中起重要作用，尽管确切机制仍未解决。在这里，我们报告人胰腺癌细胞中的 TF-因子 VIIa 复合物可产生大量 MMP-9，并促进体外侵袭能力以及体内侵袭和转移。在治疗方面，我们成功开发了一种抗人 TF 单克隆抗体，通过 TF 抑制细胞信号转导和凝血级联反应。抗体显著降低了侵袭能力和 MMP-9 的表达。该抗体不仅抑制了原位模型中的肿瘤侵袭，还抑制了门静脉注射肝转移模型中的血行转移。总之，TF-VIIa 复合物通过增强肿瘤细胞浸润能力和形成微血栓在侵袭转移中起重要作用。新建立的抗人 TF 中和抗体可能对治疗胰腺和其他侵袭性癌症有用。
