BIOCHEMICAL MECHANISM IN PLATELET-TUMOR CELL INTERACTION

血小板似乎能够促进肿瘤转移，可能是通过 物理屏蔽血小板栓塞内的肿瘤细胞， 增加与血管壁的附着，并通过提供血小板 可增强肿瘤细胞外渗和生长的因子。 以下研究旨在阐明生物化学 血小板与肿瘤相互作用的机制 细胞，并评估其在早期阶段的意义， 使用体外和体内模型系统的肿瘤转移：（i） 探讨肿瘤细胞诱导血小板生成的机制 由ADP依赖性介导的聚集， 凝血酶依赖性过程的可能作用 表面蛋白酶，补体和花生四烯酸代谢， 考虑到蜂窝协作的可能性 血小板和肿瘤细胞;（ii）人类肿瘤组织的检查 以确定是否有机制以外的 凝血酶依赖性和ADP依赖性系统可以是 检测;（iii）确定负责的血浆因子 血小板应答者和非应答者状态 用肿瘤细胞和微泡攻击的个体;（iv） ADP清除剂在减少转移中的作用的评价 （v）蛋白质的表征，以及 ADP依赖性微囊泡的糖蛋白组成 和凝血酶依赖性细胞系来确定它们是否 来自肿瘤细胞膜的专门区域;（vi） ADP依赖性和凝血酶依赖性微囊泡将被 与无反应的肿瘤细胞融合，以确定这是否可以 赋予适当的促聚集活性， 小鼠模型中的肿瘤转移;（viii）新的平行板 灌注模型将适用于研究血小板在 增强肿瘤细胞诱导的对内皮细胞的损伤， 基底膜和这些变化的生化基础。

Platelets appear able to facilitate tumor metastasis, possibly by physically shielding tumor cells within a platelet embolus, by increasing attachment to the vessel wall and by providing platelet factors which can enhance tumor cell extravasation and growth. The following studies are proposed to elucidate biochemical mechanisms involved in the interaction of platelets with tumor cells and to evaluate their significance in the early stages of tumor metastasis using in vitro and in vivo model system: (i) determine the mechanism of tumor cellinduced platelet aggregation mediated by the ADPdependent and thrombindependent processes with regard to the possible role of surface proteases, complement and arachidonate metabolism, taking into account possibilities of cellular collaboration between platelets and tumor cells; (ii) examination of human tumor tissue to determine whether mechanisms other than the thrombindependent and ADPdependent systems can be detected; (iii) identification of plasma factors responsible for responder and nonresponder status in platelets from normal individuals challenged with tumors cells and microvesicles; (iv) evaluation of the role of ADP scavengers in reducing metastasis in murine modes; (v) characterization of the protein and glycoprotein composition of microvesicles from ADPdependent and thrombindependent lines to determine whether they arise from specialized areas of the tumor cell membrane; (vi) ADPdependent and thrombindependent microvesicles will be fused with unreactive tumor cells to determine whether this can confer the appropriate proaggregatory activity and can enhance tumor metastasis in a murine model; (viii) a new parallelplate perfusion model will be adapted to study the role of platelets in enhancing tumor cellinduced damage to endothelial cells and basement membrane and the biochemical bases for these changes.