ROLE OF HEMOSTATIC FACTORS IN TUMOR BIOLOGY

该研究项目的长期目标是研究凝血系统的关键成分在肿瘤生长和转移中的作用。直到最近，还没有一个体内模型，在这种模型中，凝血系统的特定成分可以被可靠地抑制，而不会影响其他成分。具有止血因子特定缺陷的基因靶向小鼠品系的发展为此类研究打开了大门。我们建议在具有特定止血缺陷的小鼠身上探索各种体内癌症模型的生物学。目标是明确纤维蛋白原和血小板在肿瘤间质形成和肿瘤生长中的作用；明确纤维蛋白原和血小板在肿瘤转移中的作用；以及确定血小板激活、血小板与纤维蛋白原相互作用和纤维蛋白聚合物形成在肿瘤转移中所起的作用。

The long-term objective of this research project is to study the roles of key coagulation system components in tumor growth and metastasis. Until recently, an in vivo model in which specific components of the clotting system could be reliably inhibited without affecting other components has not existed. The development of gene-targeted mouse lines with specific deficits in hemostatic factors has opened the door for just such studies. We propose to explore the biology of various in vivo cancer models in mice bearing specific hemostatic deficits. The goals will be to define the role of fibrinogen and platelets in tumor stroma formation and, hence, tumor growth; define the role of fibrinogen and platelets in tumor metastasis; and to define the role played by the combination of platelet activation, platelet interaction with fibrinogen, and fibrin polymer formation in tumor metastasis.