STUDIES OF FIBRIN DEPOSITION IN CANCER

局部和全身凝血系统的激活似乎是 一种常见且重要的宿主对不断生长的肿瘤的反应。这个 这一过程的发病机制以及由此产生的重要性 纤维蛋白沉积对肿瘤生长的影响仍不确定。肿瘤细胞， 肿瘤相关巨噬细胞和肿瘤相关内皮细胞 含有具有强大促凝血活性的蛋白质(PCA)和 组织学观察到表面有纤维蛋白沉积。 原位肿瘤内肿瘤细胞和间质成分的表达。 本项目的目标是在以下方面检查这种关联 更详细，并使用特定的探测器来定义重要性 纤维蛋白致病机制中的两种主要PCA类型 在人类癌症中沉积。 利用特异性单抗(MAbs)和cDNAs探针 PCAs、细胞表面抗原和免疫调节的特异性 分子，我们将研究两个主要分子之间的相互作用 肿瘤相关蛋白、促癌物质(CP)和组织因子 (Tf)、炎性细胞和血管细胞浸润及纤维蛋白 在人类肿瘤中的沉积。我们将从以下几个方面描述PCA 从原发灶和转移灶分离的均一细胞群 这些模型中的肿瘤，利用传统的生物化学方法 以及特定的免疫和功能探针。长期的 这项研究的目标是：1)更好地了解 研究癌症中纤维蛋白沉积的机制(S)；2)发展 细胞介导的纤维蛋白的特异性抑制策略 沉积；3)表现出抑制转移形成的作用 抑制细胞介导的凝血。

Local and systemic activation of blood coagulation appears to be a common and an important host response to growing tumors. The pathogenesis of this process and the importance of the resultant fibrin deposition to tumor growth remains uncertain. Tumor cells, tumor-associated macrophages and tumor-associated endothelial cells contain proteins with potent procoagulant activities (PCAs) and fibrin deposition has been observed histologically on the surface of both tumor cells and stromal elements within tumors in situ. It is the objective of this project to examine this association in more detail and, using specific probes, to define the importance of the 2 main types of PCAs in the pathogenesis of fibrin deposition in human cancer. Utilizing specific monoclonal antibodies (mAbs) and cDNA probes specific for the PCAs, cell surface antigens and immunoregulatory molecules, we will examine the interactions between the 2 principal tumor-associated PCAs, cancer procoagulant (CP) and tissue factor (TF), inflammatory cell and vascular cell infiltration and fibrin deposition in human tumors. We will characterize the PCAs from homogeneous cell populations isolated from primary and metastatic tumors in these models, utilizing traditional biochemical methods and specific immunologic and functional probes. The long-term goals for this research are to: 1) provide a better understanding of the mechanism(s) for fibrin deposition in cancer; 2) develop strategies for the specific inhibition of cell mediated fibrin deposition; 3) demonstrate inhibition of metastasis formation by inhibiting cell-mediated clotting.