The inhibition of pancreatic cancer invasion-metastasis cascade in both cellular signal and blood coagulation cascade of tissue factor by its neutralisation antibody
The inhibition of pancreatic cancer invasion-metastasis cascade in both cellular signal and blood coagulation cascade of tissue factor by its neutralisation antibody
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DOI：
10.1016/j.ejca.2011.04.028
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发表时间：
2011-09-01
影响因子：
8.4
通讯作者：
Matsumura, Yasuhiro
中科院分区：
文献类型：
--
作者：
Saito, Yohei;Hashimoto, Yuki;Matsumura, Yasuhiro
组织因子（Tissue factor， TF）是凝血级联的起始细胞表面受体，在胰腺恶性转化中起重要作用，但其确切机制尚不清楚。在此，我们报道了TF -因子Vila复合物在人胰腺癌细胞中产生大量的MMP-9，并促进体外侵袭能力和体内侵袭转移能力。在治疗方面，我们成功开发了一种抗人TF单克隆抗体，可以抑制细胞信号传导和通过TF进行的凝血级联。该抗体显著降低了小鼠的侵袭能力和MMP-9的表达。该抗体不仅能抑制原位肝转移模型中的肿瘤侵袭，还能抑制门静脉注射肝转移模型中的血源性转移。综上所述，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发挥重要作用。新建立的抗人TF中和抗体可能对胰腺癌和其他侵袭性癌症的治疗有用。(C) 2011 Elsevier Ltd.版权所有。
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.