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

Abstract

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 γ (PPARγ)/nuclear factor-κB (NF-κB) 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)-α, 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-α, iNOS and CD86 were suppressed. In addition, treatment with OCSCs activated PPARγ and suppressed NF-κB in the Raw264.7 cells. Furthermore, the PPARγ, 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 PPARγ/NF-κB pathway.