摘要
血管新生是肿瘤发生发展中一个重要的病理特征,抗血管新生已经成为肿瘤治疗研究的一大热点。目前抗血管新生的策略主要是应用血管新生刺激因子拮抗剂或血管新生抑制因子,以恢复肿瘤中被打破的血管新生平衡。相比于血管新生刺激因子拮抗剂,内源性血管新生抑制因子展现了更好的治疗前景,但是其分子机制还有待进一步阐明。内源性血管新生抑制因子包括两类,一类是前体蛋白的水解片段,如人纤溶酶原K5(plasminogen kringle 5,K5)、血管抑素(angiostatin/kringle 1-4)、内皮抑素(endostatin)等;另一类是细胞分泌性的蛋白质,如色素上皮衍生因子(pigment epithelium-derived factor,PEDF)、激肽释放酶结合蛋白(kallikrein-binding protein,KBP/kallistatin)、抗凝血酶(antithrombin)等。本文以K5、PEDF、KBP为例,分别介绍其生物学功能、抗肿瘤血管新生机制及应用前景等方面的研究进展,希望这些研究能够为未来抗肿瘤血管新生治疗提供借鉴。
Angiogenesis is one of the important pathological characteristics in the development of tumor growth.Hence,an-ti-angiogenes is has become a hot topic in the field of cancer research.The current strategy for anti-angiogenesis therapy is to restorethe angiogenic balance which is broken in the tumor via either block of proangiogenic factorsor application of angiogenic inhibitors.Endogenous angiogenic inhibitors show more promising prospects compared with proangiogenic factor antagonists.However,the un-derlying mechanisms for the angiogenic inhibitors remain to be thoroughly elucidated.There are two kinds of endogenous angiogenicinhibitors,one is the hydrolyzed fragments of precursor protein,such as plasminogen Kringle 5（K5）,angiostatin/kringle 1~4,end-ostatin,etc;the other is cell secreted proteins,such as pigment epithelium-derived factor（PEDF）,kallikrein-binding protein（KBP/kallistatin）,antithrombin,etc.Here we summarized the research progresses on the biological functions,underlying mecha-nisms of tumor angiogenesis and application prospects of K5,PEDF,and KBP,so as to provide insights into the antiangiogenic ther-apies of tumor in the future.
出处
《中山大学学报（医学科学版）》
CAS
CSCD
北大核心
2017年第2期204-214,共11页
Journal of Sun Yat-Sen University:Medical Sciences
基金
国家自然科学基金(81272515
81572342)
科技部新药创制重大专项(2013ZX09102-053)
教育部高等学校博士学科点专项科研基金(20130171110053)
广东省自然科学基金(2014A030313073
2016A030311035)
广东省高等学校高层次人才项目
