鞘氨醇-1-磷酸与血管生成的研究进展

摘要

鞘氨醇-1-磷酸（sphingosine-1-phosphate，S1P）与细胞膜表面的G蛋白偶联受体———S1P受体（S1P receptor，S1PR）1～5结合调控下游通路，介导大部分生物学效应。越来越多的证据表明，S1P对于血管生成具有双向调控的作用，通过S1PR1、S1PR2、S1PR3调控下游信号通路，介导血管内皮细胞和血管平滑肌细胞的迁移运动及黏附作用，调节新生血管趋于稳定成熟，形成完整的血管内皮细胞屏障，同时维持新生成血管的功能完整性及稳定性等。肿瘤血管新生在肿瘤的生物学进程中起到重要作用，已有研究表明在乳腺癌、前列腺癌等恶性肿瘤模型中，抑制S1P介导的血管生成相关通路可减缓肿瘤的发生发展，而妇科肿瘤中，已有研究证实S1P参与卵巢癌的血管新生，但具体机制尚不明确，进一步的研究有望为抑制卵巢癌生长提供新的治疗方向。%Sphingosine-1-phosphate (S1P), a kind of bioactive messenger, acts via the specific cell surface G-protein-coupled receptors, S1PR1-5, to mediates various biological behaviors. Emerging evidence shows that, through S1PR1, S1PR2 and S1PR3, S1P exerts both positive and negative effects on the regulation of vascular formation, including endothelial cells movement and adhesion, vascular development, barrier protection and vascular functions. Tumor angiogenesis plays crucial roles in tumor growth. Blockade of S1P and its signaling of angiogenesis play an anti-tumor effect in breast cancer and prostate cancer. It has been proved that S1P is involved in angiogenesis of ovarian cancer but the mechanism is not clear. Further research is expected to provide new therapeutic direction to inhibit the growth of ovarian cancer.