Chemokine ligand 17 boosts the proliferation of cervical cancer cells through interleukin-27 mediated polarization of M2 macrophages

Aim Chemokine Ligand 17(CCL17), which is highly expressed in cervical cancer (CC), has been shown to significantly promote malignant progression of CC. Numerous studies have shown that M2 macrophages play a key role in tumor progression, but whether CCL17 drives CC development by inducing M2 macrophage polarization is unknown. Therefore, this study aimed to investigate whether CCL17 promotes CC progression by promoting M2 macrophage polarization.Methods The effect of CCL17 on the expression of interleukin-27 (IL-27)in CC cell line was detected by flow cytometry. The effects of CCL17 and IL-27 on proliferation and differentiation of U937 cells were analyzed. Finally, the co-culture model of macrophages and CC cells was established to detect the effects of CCL17 on the proliferation of U937 and CC cells.Results The CC cells secreted significantly higher levels of IL-27 after stimulation with CCL17. In addition, IL-27 but not CCL17 significantly upregulated interleukin 27 receptor(IL-27R) on U937 cells. IL-27 derived from CC cells can promote the proliferation of U937 cells and induce the polarization of M2 macrophages. In the co-culture system, the level of IL-27 secreted by CC cells stimulated by CCL17 was significantly increased, and both CCL17 and IL-27 promoted the proliferation of CC and U937 cells, and the effect of CCL17 was partially reversed by αIL-27.Conclusion CCL17 strengthens the crosstalk between CC cells and macrophages by increasing the secretion of IL-27 that promotes the proliferation of macrophages and induces M2 polarization, eventually contributing to the evolution of CC.