دورية أكاديمية
Human mesenchymal stem cells in the tumour microenvironment promote ovarian cancer progression: the role of platelet-activating factor
| العنوان: | Human mesenchymal stem cells in the tumour microenvironment promote ovarian cancer progression: the role of platelet-activating factor |
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| المؤلفون: | Tong Gao, Yi Yu, Qing Cong, Yisheng Wang, Mingming Sun, Liangqing Yao, Congjian Xu, Wei Jiang |
| المصدر: | BMC Cancer, Vol 18, Iss 1, Pp 1-10 (2018) |
| بيانات النشر: | BMC, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | Ovarian cancer, Mesenchymal stem cells (MSCs), Platelet-activating factor (PAF), Microenvironment, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Abstract Background The tumour microenvironment conferred by mesenchymal stem cells (MSCs) plays a key role in tumour development and progression. We previously determined that platelet-activating factor receptor (PAFR) was overexpressed in ovarian cancer cells (OCCs) and that PAF can promote ovarian cancer progression via PAF/PAFR-mediated inflammatory signalling pathways. Evidence suggests that MSCs can secrete high concentrations of PAF. Here, we investigated the role of PAF/PAFR signalling in the microenvironment mediated by MSCs and OCCs and its effect on cancer progression. Methods The PAF concentrations in the culture media of MSCs, OCCs and co-cultured MSCs and OCCs were determined by ELISA. The effects of MSCs on OCCs in vitro were assessed on cells treated with conditioned medium (CM). The expression and phosphorylation of key proteins in the PAF/PAFR signalling pathway were evaluated. In vivo, MSCs/RFP and SKOV3 cells were co-administered at different proportions to nude mice by interscapular injection. Mice in the WEB2086 group were intraperitoneally injected with the PAFR antagonist WEB2086 at a dose of 1 mg/kg.d for the duration of the animal experiments. Tumour progression was observed, and the weight and survival time of mice were measured. The PAF concentration in peripheral and tumour site blood was determined by ELISA. Results High concentrations of PAF were detected in CM from MSCs and MSCs co-cultured with OCCs. Both types of medium promoted non-mucinous OCC proliferation and migration but had no effect on mucinous-type OCCs. These effects could be blocked by PAFR inhibitors. The expression and phosphorylation of key proteins in the PAF/PAFR pathway significantly increased upon treatment with PAF and MSC-CM. In vivo, the tumour volume was larger following co-injection of SKOV3 cells and MSCs/RFP than following injection of SKOV3 cells alone. The tumour-promoting effect of MSCs/RFP was blocked by the PAFR antagonist WEB2086. Serum PAF concentrations significantly increased in co-injected mice. Conclusion Our results suggest that the tumour-promoting effect of MSCs on OCCs via their cross-talk in the tumour microenvironment was, at least in part, mediated by the PAF/PAFR pathway, suggesting a new target for the treatment of ovarian cancer. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1471-2407 68850638 |
| Relation: | http://link.springer.com/article/10.1186/s12885-018-4918-0; https://doaj.org/toc/1471-2407 |
| DOI: | 10.1186/s12885-018-4918-0 |
| URL الوصول: | https://doaj.org/article/b5d4fcd0c6f64e688506387441ed2f98 |
| رقم الأكسشن: | edsdoj.b5d4fcd0c6f64e688506387441ed2f98 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 14712407 68850638 |
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| DOI: | 10.1186/s12885-018-4918-0 |