人类间充质干细胞与卵巢癌细胞间的相互作用研究  

Direct interactions between human mesenchymal stem cells and ovarian cancer cells

作　　者：杨园园[1] 樊伯珍[1] 童晓文[1] 

机构地区：[1]同济大学附属同济医院妇产科,上海200065

出　　处：《中华医学杂志》2015年第23期1849-1853,共5页National Medical Journal of China

摘　　要：目的 通过人类间充质干细胞与卵巢癌细胞共培养方式,研究细胞与细胞间的相互作用方式.方法 用携带荧光基因第三代失活慢病毒载体感染干细胞和卵巢癌细胞,荧光显微镜下记录干细胞在肿瘤微环境中的相互作用过程,用流式细胞术研究共培养后干细胞和肿瘤细胞的细胞表面标志物表达情况;运用分子水平microarray技术,进一步提供蛋白水平表达变化的基因水平依据.结果 人脐带成功获取间充质干细胞（MSC）,成功标记的MSC和卵巢癌细胞SK-OV-3、NIH：OVCAR-3、SCCOHT-1经5-6d共培养后发现MSC促进卵巢癌细胞增殖及表达干细胞特有标志物CD90、部分CD73和CD105.发现在干细胞上有肿瘤细胞特有的CD326（EpCAM）表达.基因微阵列结果表明共培养导致不论肿瘤细胞亦或是干细胞都有大量相关基因的上调和下调.结论 人类间充质干细胞在与卵巢癌细胞相互作用的过程中明显促进卵巢癌细胞增殖,并导致卵巢癌细胞CD90及部分CD73、CD105表达升高,同时基因水平进一步支持MSC升高表达EpCAM.Objective To employ a co-culture system of human mesenchymal stem cells （MSC） and ovarian cancer cells to elucidate the cellular interactions among ovarian tumor microenvironment.Methods MSC and ovarian cancer ceils of SK-OV-3,NIH：OVCAR-3 and SCCOHT-1 were transfected with third-generation lentiviral self-inactivating （SIN） vector containing enhanced green fluorescent protein （eGFP） or mCherry gene.The interactions between MSC and ovarian cancer cells were examined by fluorescence microscopy with appropriate monochrome fluorescence filters and a FITC/TRIC dual band fluorescence filter.Flow cytometry of both cells revealed a differential expression of cell surface markers during co-culturing.Moreover,microarray was used for further analyses of gene variation during coculturing of both MSC and ovarian cancer cells.Results MSCs were successfully isolated from umbilical cords.After 5-6 days co-culturing of lentivirus eGFP-transduced human MSC with mCherry-labeled ovarian cancer cells,there was a growth stimulation of cancer cells by MSC accompanied by an induction of CD90,partial CD73 and CD105 in cancer cells and CD326 in MSC.Microarray data also showed various significant gene variations during co-culturing.Conclusion Human MSCs highly stimulate the growth and expression of CD90,partial CD73 and CD105 in ovarian cancer cells during co-culturing.And mutual cellular protein exchanges result in CD326 expression and gene alteration in MSC.

关 键 词：间充质干细胞 卵巢癌 CD90 EpCAM蛋白 

分 类 号：R737.31[医药卫生—肿瘤]