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Tumor-derived mesenchymal-stem-cell-secreted IL-6 enhances resistance to cisplatin via the STAT3 pathway in breast cancer.
| Content Provider | Europe PMC |
|---|---|
| Author | Xu, Huitao Zhou, Ying Li, Wei Zhang, Bin Zhang, Huanhuan Zhao, Shaolin Zheng, Ping Wu, Huiyi Yang, Jin |
| Copyright Year | 2018 |
| Abstract | Cisplatin is used for the treatment of a range of solid malignant tumors; however, with prolonged treatment durations, the sensitivity of tumor cells to the drug decreases owing to an unclear mechanism of drug resistance. The present study aimed to investigate whether breast-cancer-tissue-derived mesenchymal stem cells (BC-MSCs) are involved in mediating the effects of cisplatin on breast cancer cells, and which component of the BC-MSC conditioned medium (BC-MSC-CM) exhibited an anti-apoptotic effect. Cytokines/chemokines in BC-MSC-CM were quantified using a Luminex immunoassay, and reverse transcription-quantitative polymerase chain reaction analysis detected interleukin-6 (IL-6) levels in MCF-7 cells following different treatments. MTT and flow cytometry analysis measured cell vitality and apoptosis, respectively, and activation of signal transduced and activator of transcription 3 (STAT3) was evaluated by western blotting. BC-MSCs reversed the pro-apoptotic effect of cisplatin and enhanced the proliferation of MCF-7 cells more potently than bone-marrow-derived MSCs. Further study revealed that BC-MSCs secreted IL-6 to protect MCF-7 cells from apoptosis and promote their survival. Neutralizing IL-6 with a specific antibody partially inhibited the IL-6/STAT3 signaling pathway and reversed the promoter role of BC-MSCs in MCF-7 cells. Taken together, the findings of the present study indicated that BC-MSCs decreased the level of cisplatin-induced apoptosis in MCF-7 cells by activating the IL-6/STAT3 pathway in cancer cells. BC-MSCs, as important cells in the tumor microenvironment, have a key role in the treatment of breast cancer. |
| ISSN | 17921074 |
| Journal | Oncology Letters |
| Volume Number | 15 |
| PubMed Central reference number | PMC5958889 |
| Issue Number | 6 |
| PubMed reference number | 29844821 |
| e-ISSN | 17921082 |
| DOI | 10.3892/ol.2018.8463 |
| Language | English |
| Publisher | D.A. Spandidos |
| Publisher Date | 2018-04-11 |
| Access Restriction | Open |
| Rights License | This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Xu et al. |
| Subject Keyword | cisplatin breast cancer breast-cancer-derived mesenchymal stem cells apoptosis interleukin-6 tumor microenvironment |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |
