Adipose-derived mesenchymal stem cells promote cell proliferation and invasion of epithelial ovarian cancer
Adipose-derived mesenchymal stem cells promote cell proliferation and invasion of epithelial ovarian cancer
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脂肪间充质干细胞促进上皮性卵巢癌细胞增殖和侵袭
DOI：
10.1016/j.yexcr.2015.07.020
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发表时间：
2015-09-10
影响因子：
3.7
通讯作者：
Wang, Zehua
中科院分区：
文献类型：
--
作者：
Chu, Yijing;Tang, Huijuan;Wang, Zehua
脂肪间充质干细胞（ADSC）是肿瘤微环境的重要组成部分。然而，ADSC是否参与卵巢癌的进展仍不清楚。在这项研究中，我们研究了来自正常供体网膜的人ADSC对人上皮性卵巢癌（EOC）细胞的体外和体内影响。建立ADSCs与人EOC细胞直接和间接共培养模型，采用EdU掺入法和流式细胞仪检测ADSCs对EOC细胞增殖的影响。通过Transwell迁移实验和MMPs检测来评估EOC细胞的体外侵袭活性。通过腹腔内注射EOC细胞（伴随或不伴随ADSC）建立小鼠模型，以研究ADSC在体内肿瘤进展中的作用。我们发现，ADSCs显着促进EOC细胞的增殖和侵袭在直接和间接的共培养实验。此外，与ADSCs共培养后，EOC细胞分泌更高水平的基质金属蛋白酶（MMP），抑制MMP 2和MMP 9可部分缓解ADSCs的促肿瘤作用。在小鼠异种移植模型中，我们证实ADSC促进EOC的生长和转移，并提高MMP 2和MMP 9的表达。我们的研究结果表明，网膜脂肪干细胞在卵巢癌的进展中起促进作用。(C)2015爱思唯尔公司All rights reserved.
Adipose-derived mesenchymal stem cell (ADSC) is an important component of tumor microenvironment. However, whether ADSCs have a hand in ovarian cancer progression remains unclear. In this study, we investigated the impact of human ADSCs derived from the omentum of normal donors on human epithelial ovarian cancer (EOC) cells in vitro and in vivo. Direct and indirect co-culture models including ADSCs and human EOC cell lines were established and the effects of ADSCs on EOC cell proliferation were evaluated by EdU incorporation and flow cytometry. Transwell migration assays and detection of MMPs were performed to assess the invasion activity of EOC cells in vitro. Mouse models were established by intraperitoneal injection of EOC cells with or without concomitant ADSCs to investigate the role of ADSCs in tumor progression in vivo. We found that ADSCs significantly promoted proliferation and invasion of EOC cells in both direct and indirect co-culture assays. In addition, after co-culture with ADSCs, EOC cells secreted higher levels of matrix metalloproteinases (MMPs), and inhibition of MMP2 and MMP9 partially relieved the tumor-promoting effects of ADSCs in vitro. In mouse xenograft models, we confirmed that ADSCs promoted EOC growth and metastasis and elevated the expression of MMP2 and MMP9. Our findings indicate that omental ADSCs play a promotive role during ovarian cancer progression. (C) 2015 Elsevier Inc. All rights reserved.