TNFSF15对肿瘤脉管生成调控的临床意义及研究进展

Clinical Significance and Advances of TNFSF15 Modulation on Tumor Angiogenesis and Lymphangiogenesis

肿瘤坏死因子超家族成员15(TNFSF15)主要是由血管内皮细胞特异分泌的细胞因子。作为死亡受体3(DR3)的配体,它参与调控VEGF/VEGFR信号通路,进而影响多种脉管细胞的生理及病理过程,例如抑制血管内皮细胞增殖、促进树突状细胞成熟、促进淋巴内皮细胞增殖和迁移、防止血管渗漏、抑制血管生成等。临床研究数据表明TNFSF15启动子区域突变引起的TNFSF15高表达会增加罹患多种肿瘤的风险。然而,TNFSF15对血管和淋巴管生成的影响截然相反,其可通过结合血管内皮细胞表面受体DR3抑制肿瘤内血管生成而抑制肿瘤生长,但与淋巴内皮细胞表面受体DR3结合后反导致肿瘤内淋巴管生成而促进肿瘤淋巴转移。分析其不同生物效应对肿瘤脉管生成治疗有一定临床意义,本文仅就此作一综述。

Tumor necrosis factor superfamily member 15(TNFSF15),a cytokine produced largely by vascular endothelial cells,is involved in various activities of physiological and pathological processes via regulating VEGF/VEGFR signal pathways.For example,it specifically inhibits the proliferation of vascular endothelial cells,promotes the maturation of dendritic cells,promotes the proliferation and migration of lymphatic endothelial cells,prevents vascular leakage,inhibits angiogenesis and so on.Clinical data show that high expression of TNFSF15 caused by mutations in the TNFSF15 promoter region increases the risk of a variety of tumors.In addition,it is worth noting that TNFSF15 has the opposite effect on angiogenesis and lymphangiogenesis.This paper briefly reviews the different biological effects of TNFSF15 on tumor vascular system.