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人脂肪来源干细胞的脂肪生成诱导对MCF-7人乳腺癌细胞侵袭能力的旁分泌调节。

Human adipose-derived stem cell adipogenesis induces paracrine regulation of the invasive ability of MCF-7 human breast cancer cells .

作者信息

Zhao Yang, Gao Jianhua, Lu Feng

机构信息

Department of Plastic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

出版信息

Exp Ther Med. 2013 Oct;6(4):937-942. doi: 10.3892/etm.2013.1237. Epub 2013 Jul 30.

Abstract

The aim of this study was to determine the effects of paracrine regulation on the invasive ability of MCF-7 human breast cancer cells through human adipose-derived stem cell (hADSC) adipogenesis. hADSC differentiation of the third and fourth passages of cells was induced in different induction media: osteogenic, adipogenic and chondrogenic. Transwell migration assays in the differently conditioned media, flow cytometry, enzyme-linked immunosorbent assay and western blot analysis for selected cytokines were performed. The flow cytometric analysis demonstrated positive expression of CD29, CD44 and CD105, while expression of CD34 and CD45 was not identified. The transwell migration assay showed that the invasive ability of MCF-7 cells was significantly enhanced during hADSC adipogenesis. hADSCs exerted a significantly positive effect on the invasive activity of MCF-7 cells during adipo-genesis. The results indicate that the high expression levels of activating protein 2 (aP2) in MCF-7 and adipocytes induced for 12 days may be associated with cell growth, invasion and metastasis. Peroxisome proliferator-activated receptor γ may be involved in fatty syntheses during adipogenic initiation and following adipogenic differentiation, possibly acting as a protection factor resulting in cell maturation and differentiation. This study also demonstrated that the expression of vascular endothelial growth factor was repressed by hADSCs, while that of matrix metalloproteinase-2 and urokinase-type plasminogen activator was increased to a significant level.

摘要

本研究的目的是通过人脂肪来源干细胞(hADSC)的成脂作用来确定旁分泌调节对MCF-7人乳腺癌细胞侵袭能力的影响。在不同的诱导培养基中诱导细胞第三和第四代的hADSC分化:成骨、成脂和软骨生成。对不同条件培养基进行Transwell迁移试验、流式细胞术、酶联免疫吸附测定以及对选定细胞因子进行蛋白质印迹分析。流式细胞术分析显示CD29、CD44和CD105呈阳性表达,而未检测到CD34和CD45的表达。Transwell迁移试验表明,在hADSC成脂过程中MCF-7细胞的侵袭能力显著增强。在成脂过程中,hADSCs对MCF-7细胞的侵袭活性产生显著的正向影响。结果表明,MCF-7和成脂诱导12天的脂肪细胞中激活蛋白2(aP2)的高表达水平可能与细胞生长、侵袭和转移有关。过氧化物酶体增殖物激活受体γ可能参与成脂起始和成脂分化后的脂肪合成,可能作为一种保护因子导致细胞成熟和分化。本研究还表明,hADSCs抑制血管内皮生长因子的表达,而基质金属蛋白酶-2和尿激酶型纤溶酶原激活剂的表达则显著增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9e5/3797295/72182243af0d/ETM-06-04-0937-g00.jpg

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