Plasticity of patient-matched normal mammary epithelial cells is dependent on autologous adipose-derived stem cells

Plasticity of patient-matched normal mammary epithelial cells is dependent on autologous adipose-derived stem cells
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DOI:
10.1038/s41598-019-47224-2
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发表时间:
2019-07-24
期刊:
影响因子:
4.6
通讯作者:
Boos, Anja M.
Boos, Anja M.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kengelbach-Weigand, Annika;Tasbihi, Kereshmeh;Boos, Anja M.

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随着脂肪干细胞(adipose-derived stem cells,ADSC)临床应用的日益广泛,近年来,ADSC在临床上的应用越来越广泛。G.本研究旨在获得关于ADSC对乳腺组织重塑的影响的新见解,并确定影响脂肪转移的患者依赖性因素,以及开始解决其肿瘤风险。ADSC分泌组分析了五个正常的乳房缩小患者,并含有高水平的生长因子,细胞因子和蛋白质介导的入侵。ADSC/ADSC分泌体使用细胞培养测定法测试其对原代乳腺上皮细胞和肿瘤上皮细胞的功能的影响。ADSC/ADSC分泌组显著刺激原代正常和肿瘤上皮细胞的增殖、迁移和三维侵袭。IL-6显著诱导EMT和侵袭。ADSC分泌组显著上调正常上皮细胞基因表达,包括MMPs和ECM受体。我们的研究支持ADSC及其分泌组通过改变微环境促进正常乳腺组织重塑的有利条件。并且对于手术后残留的乳腺癌细胞也可能是重要的。
Due to the increasing clinical application of adipose-derived stem cells (ADSC), e. g. lipotransfer for breast reconstruction, this study aimed to gain novel insights regarding ADSC influence on breast tissue remodeling and determine patient-dependent factors affecting lipotransfer as well as begin to address its oncological risks. The ADSC secretome was analyzed from five normal breast reduction patients and contained elevated levels of growth factors, cytokines and proteins mediating invasion. ADSC/ADSC secretomes were tested for their influence on the function of primary mammary epithelial cells, and tumor epithelial cells using cell culture assays. ADSC/ADSC secretomes significantly stimulated proliferation, transmigration and 3D-invasion of primary normal and tumor epithelial cells. IL-6 significantly induced an EMT and invasion. The ADSC secretome significantly upregulated normal epithelial cell gene expression including MMPs and ECM receptors. Our study supports that ADSC and its secretome promote favorable conditions for normal breast tissue remodeling by changing the microenvironment. and may also be important regarding residual breast cancer cells following surgery.