Ovarian cancer stem cells induce the M2 polarization of macrophages through the PPARγ and NF-κB pathways

被引:58
作者
Deng, Xinchao [1 ]
Zhang, Ping [1 ]
Liang, Tingting [1 ]
Deng, Suye [2 ]
Chen, Xiaojie [1 ]
Zhu, Lin [1 ]
机构
[1] Shandong Univ, Hosp 2, Dept Obstet & Gynaecol, Jinan 250033, Shandong, Peoples R China
[2] Hosp Pingdu Tradit Chinese Med, Pingdu 266700, Shandong, Peoples R China
关键词
ovarian cancer stem cells; macrophages; M1/M2; polarization; peroxisome proliferator-activated receptor gamma; nuclear factor-kappa B; PROLIFERATOR-ACTIVATED RECEPTORS; TUMOR MICROENVIRONMENT; EXTRACELLULAR-MATRIX; EXPRESSION; CONTRIBUTE; APOPTOSIS; IMPACT;
D O I
10.3892/ijmm.2015.2230
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Increasing evidence suggests an association between cancer stem cells and the tumor microenvironment. Ovarian cancer stem cell (OCSC) factors can influence the tumor microenvironment and prognosis. However, the effects of OCSCs on macrophage M1/M2 polarization are not yet completely understood. In the present study, we evaluated the effects of OCSCs on macrophage M1/M2 polarization. In addition, we investigated whether the activation of the peroxisome proliferator-activated receptor. (PPAR gamma)/nuclear factor-kappa B (NF-kappa B) pathway is involved in these effects, thus modulating the M1/M2 differentiation of monocytes into macrophages. The expression levels of markers of the M1 state, such as tumor necrosis factor (TNF)-alpha, inducible nitric oxide synthase (iNOS) and CD86, as well as those of markers of M2 activation, such as mannose receptor (MR), interleukin (IL)-10 and arginase-1 (Arg-1), were measured by RT-qPCR. We found that the OCSCs promoted the M2 polarization of Raw264.7 macrophages by upregulating the expression of MR, IL-10 and Arg-1, while the expression levels of M1 macrophages markers, including TNF-alpha, iNOS and CD86 were suppressed. In addition, treatment with OCSCs activated PPAR gamma and suppressed NF-kappa B in the Raw264.7 cells. Furthermore, the PPAR gamma, antagonist GW9662, attenuated the promoting effects of OCSCs on the M2 polarization of macrophages. To the best of our knowledge, the findings of the present study, provide the first evidence that OCSCs promote the M2 polarization of macrophages through the PPAR gamma/NF-kappa B pathway.
引用
收藏
页码:449 / 454
页数:6
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