Anti-coagulant Factors Inhibits the Metastatic Activity of Tumor Cells

通过研究抗凝因子表达与胰腺肿瘤细胞BxPC-3、MIA PaCa-1、PANC-2转移活性的关系，得到如下结果：1。使用趋化室测量肿瘤转移活性，该室由一种包被滤膜的细胞外基质分开，高度依赖于基质的组成，BxPC-3和MIA PaCa-1细胞分别倾向于明胶和玻璃粘连蛋白。BxPC-3细胞连续表达血栓调节素？和组织因子（TF）， TNF-α、IL-1β、PMA等多种药物治疗后，TM和TF分别降低和升高，与侵袭活性相关。抗tm IgG和抗tf IgG分别作用于BxPC-3细胞后，细胞活性升高和降低，而抗tf途径抑制剂IgG作用于MIA PaCa-1细胞后，细胞活性无明显变化。利用TM的单克隆抗体，我们认为TM对肿瘤逆转的抑制活性与可以与蛋白C相互作用的结构域有关。然而，激活的蛋白C和Va因子的降解产物都没有抑制肿瘤逆转。将TM表达质粒转染到未表达TM的MIA PaCa-1细胞中，导致细胞侵袭活性呈剂量依赖性降低。因子X和Xa对肿瘤细胞的转移活性没有增强作用，而因子VIIa对肿瘤细胞的转移活性有增强作用。抗- vii IgG预处理可阻断肿瘤转移过程中tnf依赖性的增加，提示tnf - viia复合物直接参与细胞内信号通路介导基质金属蛋白酶的表达。

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.