Anti-coagulant Factors Inhibits the Metastatic Activity of Tumor Cells

抗凝因子抑制肿瘤细胞的转移活性

• 批准号: 10672055
• 负责人: HORIE Shuichi
• 金额: $ 2.05万
• 依托单位: Teikyo 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-10672055/
• 关键词: Anticoagulation Factors; Tumor Cells; Cancer; Metastasis; Thrombomodulin; Tissue Factor; Extracellular matrix; Antibody

By studies on the relation between expressions of anti-coagulant factors and metastatic activities of pancreatic tumor cells, BxPC-3, MIA PaCa-1, and PANC-2, following results were obtained.1. Tumor metastatic activity measured by use of chemotaxis chamber, which was divided by a kind of extracellular matrix coated on a filter, was highly dependent on the composition of the matrix, and BxPC-3 and MIA PaCa-1 cells prefer gelatin and vitronectin, respectively, for their inversion.2. BxPC-3 cells expressed continuously both thrombomodulin ? and tissue factor (TF), and the decrease and the increase in TM and TF, respectively, caused by treatment with various agents, such as TNF-α, IL-1β and PMA, correlated to the invasive activity.3. Treatment of BxPC-3 cells with anti-TM IgG and anti-TF IgG increased and decreased, respectively, the activity of the cells, whereas none of change was observed in MIA PaCa-1 cells treated with anti-TF pathway inhibitor IgG. Using monoclonal antibodies of TM, the inhibitory activity of TM against tumor inversion was thought to be associated with the domain that could be interacted with protein C. However, both activated protein C and degradation products of factor Va did not inhibit the tumor inversion.4. Transfection of expression plasmid of TM into MIA PaCa-1 cells, those were not expressed TM, resulted in does-dependent decrease in the invasive activity of the cells.5. Factor X and Xa did not enhance the metastatic activity of tumor cells, while factor VIIa increased the activity. The TF-dependent increase in the metastasis was blocked by the pretreatment with anti-VII IgG, indicating that the complex of TF-VIIa involved directly in intracellular signaling for the expression of matrix metalloproteases.

通过对胰腺癌细胞BxPC-3、MIA PaCa-1和PANC-2的抗凝血因子表达与转移活性关系的研究，得到以下结果.通过使用被一种包被在过滤器上的细胞外基质分隔的趋化室测量的肿瘤转移活性高度依赖于基质的组成，并且BxPC-3和MIA PaCa-1细胞分别偏好明胶和玻连蛋白用于其逆转. BxPC-3细胞持续表达血栓调节蛋白？TNF-α、IL-1β和PMA治疗后，TM和TF的降低和升高与侵袭性有关.用抗TM IgG和抗TF IgG处理BxPC-3细胞分别增加和降低细胞的活性，而在用抗TF途径抑制剂IgG处理的MIA PaCa-1细胞中没有观察到变化。利用TM的单克隆抗体，TM对肿瘤转化的抑制活性被认为与可与蛋白C相互作用的结构域有关。而活化蛋白C和Va因子降解产物均不能抑制肿瘤的转化.将TM的表达质粒转染到不表达TM的MIA PaCa-1细胞中，可使其侵袭活性呈剂量依赖性降低.因子X和Xa不增强肿瘤细胞的转移活性，而因子VIIa增强活性。TF依赖性增加的转移被阻断的预处理与抗-VII IgG，表明TF-VIIa的复合物直接参与细胞内信号传导的基质金属蛋白酶的表达。