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 通过以下方式在血小板栓子内物理屏蔽肿瘤细胞 增加对血管壁的附着性并通过提供血小板 可促进肿瘤细胞外渗和生长的因子。 建议进行以下研究来阐明生物化学 血小板与肿瘤相互作用机制的研究进展 并评估它们在早期阶段的意义。 利用体外和体内肿瘤转移模型系统：(一) 确定肿瘤细胞诱导血小板的机制 ADP依赖和ADP受体介导的聚集 血栓非依赖性过程中的可能作用 表面蛋白、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)人体肿瘤组织的检查 要确定是否存在 血栓非依赖性和ADP依赖性系统可以 检测到；(3)确定血浆因素对 正常血小板的应答者和非应答者状态 被肿瘤细胞和微泡挑战的个体；(Iv) 腺苷二磷酸清除剂在减少转移中的作用评价 在小鼠模式中；(V)蛋白质和 ADP依赖型微囊的糖蛋白组成 和血栓非依赖线，以确定它们是否出现 来自肿瘤细胞膜的专门领域；(Vi) 依赖于ADP和不依赖于血栓的微囊将 与无反应的肿瘤细胞融合以确定这是否可以 授予适当的促凝集活动，并可以增强 小鼠肿瘤转移模型；(Viii)一种新的平行四边形 将采用灌流模型来研究血小板在 增强肿瘤细胞对内皮细胞的损伤作用 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.