缺氧激发卵巢癌上皮性肿瘤细胞中的干细胞向内皮样细胞分化  

The differentiation of stem cells to endothelial-like cells in epithelial ovarian cancer cells evoked by hypoxia

作　　者：竺鹏飞[1,2] 丰有吉[1] 尧良清[1] 陈默[1] 徐丛剑[1] 王丽[3] 陈思锋[3] 

机构地区：[1]复旦大学附属妇产科医院妇科,上海200001 [2]浙江省上虞市人民医院妇产科,上虞312300 [3]复旦大学医学院生理与病理生理学系,上海200032

出　　处：《复旦学报（医学版）》2010年第4期418-421,共4页Fudan University Journal of Medical Sciences

摘　　要：目的在缺氧状态下对卵巢癌上皮性肿瘤细胞SKOV-3和ES-2诱导的内皮样细胞(endothelial-likecell,EC-like)进行鉴定,寻找卵巢癌上皮性肿瘤干细胞(tumor stemcell,TSC)的线索。方法建立Matrigel三维培养系统,在1%O2缺氧条件下对卵巢癌上皮性肿瘤细胞SKOV-3和ES-2进行缺氧诱导。应用免疫荧光双重标记、透射电镜等技术对SKOV-3和EC-2来源内皮样细胞的表面特异性抗原、超微结构和乙酰化低密度脂蛋白(acetylated lowdensity lipoprotein,acLDL)吞噬功能进行鉴定。结果培养7天后,SKOV-3内皮样细胞可以表达Flk-1、AC133及v WF;细胞出现空泡样变化,表面出现微绒毛样突起,极少数细胞出现质膜包裹的颗粒。ES-2内皮样细胞可以表达Flk-1、CD34;细胞出现空泡样变化,表面出现微绒毛样突起,极少数细胞出现质膜包裹的颗粒;部分Dil阳性细胞,具有吞噬acLDL功能。常氧状态下无上述变化。结论卵巢癌肿瘤细胞具有干细胞(stemcell,SC)特征:SKOV-3和ES-2内皮样细胞可能来源于卵巢癌上皮性肿瘤细胞中的SC。缺氧的压力下卵巢癌SC先向血管内皮样细胞分化,说明卵巢癌SC是一种可向内皮细胞(endothelial cell,EC)分化的肿瘤源性EC前期细胞。缺氧激发下卵巢癌SC分化的EC-like更类似内皮祖细胞(endothelial progenitor cells,EPC)而非EC。Objective To inentify endothelial-like cells（EC-like） induced from SKOV-3 and ES-2 ovarin cancer cell lines under the hypoxic condition,and to collect dues for ovarian tumor stem cell（TSC）. Methods The 3-dimension culture system with Matrigel was established to cultivate SKOV-3 and ES-2 ovarian cancer cell lines under the hypoxic condition of 1% O2.Immunofluorescence markers and transmission electron microscopes was used to investigate the specific surface antigens,the ultrastructure and the phagocytosis of acetylated low-density lipoprotein（Ac-LDL） of induced EC-like cancer cells. Results After 7 days of culture,EC-like SKOV-3 cells could express Flk-1,AC133 and vWF.Vacuolar degeneration,microvillus-like protuberance and rare membrane-wrapped particles were observed.EC-like ES-2 cells could express Flk-1 and CD34,and a proportion of these cells showed local cytoplasmic positivity for Dil,which were able to phagocytose Ac-LDL.The above phenomena could not be observed under normxia. Conclusions Ovarian cancer cells possess stem-like characteristics： EC-like SKOV-3 and ES-2 cells may derive from the TSCs in ovarian carcinoma.Under the stress of hypoxia,ovarian cancer stem cells preferentially differentiate towards EC-like cells,thus it can be considered as tumor-derived endothelial cells（EC） precursor cells.Ovarian cancer-derived EC-like cells are more alike with endothelial progenitor cells（EPC） rather than ECs,which provide a new target for anti-vascular therapy.

关 键 词：卵巢癌 干细胞 缺氧 内皮样细胞 抗原 

分 类 号：R737.31[医药卫生—肿瘤]