ROLE OF HEMOSTATIC FACTORS IN TUMOR BIOLOGY

本研究项目的长期目标是研究关键凝血系统成分在肿瘤生长和转移中的作用。直到最近，还不存在一种体内模型，可以在不影响其他成分的情况下可靠地抑制凝血系统的特定成分。具有止血因子特异性缺陷的基因靶向小鼠系的发展为这类研究打开了大门。我们建议在具有特异性止血缺陷的小鼠中探索各种体内癌症模型的生物学。目标是确定纤维蛋白原和血小板在肿瘤基质形成中的作用，从而确定肿瘤生长；明确纤维蛋白原和血小板在肿瘤转移中的作用；并明确血小板活化、血小板与纤维蛋白原相互作用、纤维蛋白聚合物形成联合作用在肿瘤转移中的作用。

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.