溶血磷脂酸在卵巢癌进展中的机制研究

Mechanisms of Lysophosphatidic Acid Involved in the Progression of Ovarian Cancer

在卵巢癌的发生发展中,脂代谢发挥重要作用,溶血磷脂酸(LPA)作为一种生物活性磷脂分子,通过与多种G蛋白偶联受体结合,参与卵巢癌的增殖、转移和侵袭活动。一方面,LPA可通过促进肿瘤血管新生、调节细胞周期、抑制凋亡、促进糖代谢及维持肿瘤干细胞(CSC)的特性来促进卵巢癌细胞增殖;另一方面,LPA可增加基质金属蛋白酶(MMP)及尿激酶型纤溶酶原激活物(u PA)的表达、干预细胞间连接和骨架蛋白、促进上皮-间质转化(EMT),进而促进卵巢癌的转移和侵袭。此外,卵巢癌患者血浆中高水平的LPA单独或与卵巢癌的其他肿瘤标记物联合检测具有更高的敏感度和特异度。综述LPA在卵巢癌增殖、转移和侵袭中的作用机制以及潜在的诊断、治疗靶点方面的研究进展。

In the development of ovarian cancer,the aberrant lipid metabolism plays a critical role.Lysophosphatidic acid（LPA）,a bioactive molecular,can bind to different G protein-coupled receptors and stimulate the proliferation,metastasis and invasion of ovarian cancer.On one hand,LPA could stimulate proliferation by promoting angiogenesis,regulating cell cycle,inhibiting apoptosis,promoting glucose metabolism and maintaining cancer stem cell（CSC） characteristics.On the other hand,LPA could stimulate the metastasis and invasion by enhancing the expression of matrix metalloproteinases（MMPs） and urokinase-type plasminogen activator（u PA）,interfering intercellular junctions and cytoskeletons and inducing epithelial-mesenchymal transition（EMT）.Besides,testing plasma level of LPA alone or combining with other tumor biomarkers is more sensitive and specific.In this article,we review the latest knowledge on the molecular mechanism of LPA in the proliferation,migration and invasion of ovarian cancer as well as potential biological targets.