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脂肪组织来源干细胞分泌的CXCL5促进癌细胞增殖。

CXCL5 secreted from adipose tissue-derived stem cells promotes cancer cell proliferation.

作者信息

Zhao Yuying, Zhang Xiaosan, Zhao Hong, Wang Jingxuan, Zhang Qingyuan

机构信息

Department of Medical Oncology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.

出版信息

Oncol Lett. 2018 Feb;15(2):1403-1410. doi: 10.3892/ol.2017.7522. Epub 2017 Dec 5.

Abstract

Accumulating data suggest that adipose tissue facilitates breast tumor initiation and progression through paracrine and endocrine pathways, and that adipose tissue-derived stem cell (ASC) is likely the major cell type responsible for tumorigenesis and tumor development. However, it remains unknown how ASCs exert their effects. In the present study, in cultured breast cancer cell lines, including estrogen receptor (ER)-positive MCF-7 cells and ER-negative MDA-MB-231 cells, the effects on tumor proliferation of isolated ASCs from human breasts were examined. The expression of 174 cytokines was additionally identified in this medium. With an anti-human C-X-C motif ligand 5 (CXCL5) monoclonal antibody, the effects of neutralization of CXCL5 on the actions of ASCs in a co-culture medium of ASCs and tumor cells were studied The results demonstrated that ASCs significantly increased the number of breast cancer cells compared with controls. Similarly, the co-culture medium of ASCs with breast cancer cells exhibited potent effects on tumor cell proliferation. In the co-culture medium of ASCs with breast cancer cells, CXCL5 levels were significantly increased. In addition, depletion of CXCL5 with its specific antibody in ASC-conditioned medium blocked the stimulatory effect of ASCs on the proliferation of breast cancer cells. To the best of our knowledge, these results indicate for the first time that ASC-secreted CXCL5 is a key factor promoting breast tumor cell proliferation.

摘要

越来越多的数据表明,脂肪组织通过旁分泌和内分泌途径促进乳腺肿瘤的起始和进展,并且脂肪组织来源的干细胞(ASC)可能是负责肿瘤发生和肿瘤发展的主要细胞类型。然而,ASC如何发挥其作用仍不清楚。在本研究中,在包括雌激素受体(ER)阳性的MCF-7细胞和ER阴性的MDA-MB-231细胞在内的培养乳腺癌细胞系中,检测了从人乳房分离的ASC对肿瘤增殖的影响。此外,在这种培养基中鉴定了174种细胞因子的表达。使用抗人C-X-C基序配体5(CXCL5)单克隆抗体,研究了中和CXCL5对ASC与肿瘤细胞共培养基中ASC作用的影响。结果表明,与对照组相比,ASC显著增加了乳腺癌细胞的数量。同样,ASC与乳腺癌细胞的共培养基对肿瘤细胞增殖表现出强大的作用。在ASC与乳腺癌细胞的共培养基中,CXCL5水平显著升高。此外,在ASC条件培养基中用其特异性抗体耗尽CXCL5可阻断ASC对乳腺癌细胞增殖的刺激作用。据我们所知,这些结果首次表明ASC分泌的CXCL5是促进乳腺肿瘤细胞增殖的关键因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b46/5777118/8225be59e868/ol-15-02-1403-g00.jpg

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