凝血酶及肿瘤转移.docVIP

凝血酶及肿瘤转移 　 作者：孟宇宏,虞积耀,陆应麟 【摘要】 　　凝血酶是一种多功能丝氨酸蛋白酶，在体内一系列生理和病理过程中起重要作用。它不但参与止血和凝血、炎症、免疫反应、组织修复和创伤愈合，而且可激活正常细胞的致瘤潜能和导致恶性细胞的转移表型。凝血酶是肿瘤细胞的促有丝分裂剂，能够增强肿瘤细胞对细胞因子的增殖反应，增强肿瘤细胞对血小板的黏附及体外细胞基质的侵袭，促进肿瘤血管形成和肿瘤微环境的组织重建。凝血酶受体家族 PARs介导凝血酶的细胞生物学效应。凝血酶对肿瘤细胞生长具有双向调控作用，低浓度者促进生长，高浓度者抑制生长，甚至导致肿瘤细胞凋亡。本文就凝血酶的生物学功能、凝血酶与肿瘤及凝血酶受体等进行综述。 【关键词】 凝血酶　肿瘤；肿瘤转移 　　Thrombin and Tumor Metastasis ——Review Abstract Thrombin is a multifunctional serine protease that plays a key role in a variety of physiological and pathological conditions. In addition to the role in hemostasis and coagulation, thrombin has other numerous biological activities affecting inflammation, immune responses, tissue repair and wound healing. Apart from its physiological role thrombin activates the oncogenic potential of both normal and malignant cells and leads a metastatic phenotype. It is a potent mitogen for many tumor cells. It potentiates the proliferative response of tumor cells to some growth factors, increases the adhesive properties to the platelets and invasion processes of tumor cells to the extracellular matrix, enhances the metastatic capacity of tumor cells，activates angiogenesis and remodels the microenvironment of the tumor. The cellular biological effects of thrombin are mediated at least in part by a new subfamily of Gproteincoupled receptors designated proteinaseactivited receptors（PARs）. Thrombin has a bilateral effect on tumor cells:enhanced growth at low concentration, impaired growth/apoptosis at higher concentration. In this papers, the biological function of thrombin, thrombin and tumors, and thrombin receptors etc were reviewed. Key words thrombin； tumor ；metastasis 侵袭和转移是恶性肿瘤的基本生物学特征，也是肿瘤患者死亡的主要原因。肿瘤的侵袭和转移是肿瘤细胞、宿主细胞和组织微环境之间一系列复杂、多步骤、多因素、多功能的相互作用的序贯连续过程。此过程涉及到多种成分（肿瘤细胞、宿主细胞、细胞外基质）、多种细胞功能（黏附作用、降解作用、运动作用）及多种基因（转移抑制基因、黏附分子及其受体、细胞外基质降解酶、运动因子、趋化因子等）。细胞外基质的重塑是肿瘤局部侵袭的必需环节，细胞外基质成分的降解是完成转移的关键步骤之一。在肿瘤侵袭和转移过程中，各种蛋白酶与其表面特异性受体组成的细胞外蛋白分解系统被周密的调节以适应细胞功能和降解选择性的基质屏障。 众所周知，血栓形成是恶性肿瘤常见的并发症，而血栓形成与癌症播散之间的因果关系最近越来越多地为人们