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Protease inhibitor PP5/TFP1-2 expression in breast cancer

乳腺癌中蛋白酶抑制剂 PP5/TFP1-2 的表达

基本信息

批准号：
10671126
负责人：
ISHIKAWA Takashi
金额：
$ 1.22万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671126/
关键词：
PP5 TFPI-2 Serine Protease Inhibitor Breast Cancer Tissue Factor blood-clotting system pp5 TFPL-2 セリンプロテアーゼインヒビター

项目摘要

Recently, there are many reports demonstrating that blood-clotting system is closely involved in the mechanism of cancer invasion and metastasis. Tissue factor (TF) initiates blood clotting by direct activation of factor X in association with factor VIIa. TF is known to be important not only in blood clotting but also in development of vascular system, angiogenesis or production of VEGF. We demonstrated that 1) TF cytoplasmic tail communicates with action cytoskeleton via an action binding protein ABP280, 2) TF expressing tumor cells obtain elevated capacity of cell adhesion and migration in factor VIIa or anti-TF antibody dependent manner, 3) TF mediated adhesion induced phosphorylation of focal adhesion kinase (FAK). We further obtained several important findings by immunohistochemical studies on bladder cancer tissues. TF expression was observed in cancer cells, especially in invasion front, and factor VIIa immunoreactivity was demonstrated around small vessels of invasion front, which may come from blood. One could speculate that TF expressing cancer cells may migrate towards vessels by factor VIIa around them and this system may be involved in the intravasation step of cancer metastasis. We also evaluated the expression of TFPI-1 and TFPI-2, which are native inhibitors of factor X activation by TF, in surgically resected breast cancer tissues in combination with non-cancerous tissues by RT-PCR. Expression of TFPI-2 seemed to be attenuated in cancer tissues. Immunohistological studies for TF in combination with TFPIs in breast cancer tissues should be needed.

近年来，越来越多的研究报道表明，凝血系统与肿瘤的侵袭转移机制密切相关。组织因子（TF）通过直接激活因子X和因子VIIa来启动血液凝固。众所周知，TF不仅在血液凝固过程中起重要作用，而且在血管系统的发育、血管生成或VEGF的产生中也起重要作用。结果表明：1)TF细胞质尾部通过作用结合蛋白ABP280与作用细胞骨架进行通信；2)表达TF的肿瘤细胞通过因子VIIa或抗TF抗体依赖的方式获得细胞粘附和迁移能力的提高；3)TF介导的粘附诱导局灶黏附激酶（FAK）的磷酸化。我们进一步通过对膀胱癌组织的免疫组化研究获得了一些重要的发现。TF在癌细胞中表达，尤其是在侵袭前，并且在侵袭前的小血管周围显示VIIa因子的免疫反应性，可能来自血液。我们可以推测，表达TF的癌细胞可能通过其周围的VIIa因子向血管迁移，该系统可能参与了癌症转移的内渗步骤。我们还通过RT-PCR评估了TFPI-1和TFPI-2的表达，TFPI-1和TFPI-2是TF激活因子X的天然抑制剂，在手术切除的乳腺癌组织与非癌组织联合中表达。TFPI-2在癌组织中的表达似乎减弱。需要对乳腺癌组织中TF联合tfpi的免疫组织学研究。