CCL8 secreted by tumor-associated macrophages promotes invasion and stemness of glioblastoma cells via ERK1/2 signaling

Abstract

Tumor-associated macrophages (TAMs) constitute a large population of glioblastoma and facilitate tumor growth and invasion of tumor cells, but the underlying mechanism remains undefined. In this study, we demonstrate that chemokine (C-C motif) ligand 8 (CCL8) is highly expressed by TAMs and contributes to pseudopodia formation by GBM cells. The presence of CCL8 in the glioma microenvironment promotes progression of tumor cells. Moreover, CCL8 induces invasion and stem-like traits of GBM cells, and CCR1 and CCR5 are the main receptors that mediate CCL8-induced biological behavior. Finally, CCL8 dramatically activates ERK1/2 phosphorylation in GBM cells, and blocking TAM-secreted CCL8 by neutralized antibody significantly decreases invasion of glioma cells. Taken together, our data reveal that CCL8 is a TAM-associated factor to mediate invasion and stemness of GBM, and targeting CCL8 may provide an insight strategy for GBM treatment.

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Acknowledgements

This work was supported by the grants from the National Science Foundation of China (81773145 and 81372273) to XZ, the National Key Research and Development Program of China (2017YFC1309004 to XZ and 2016YFA0101203 to XWB) and the Basic and Applied Fund of First Affiliated Hospital of Army Military Medical University (SWH2016JCZD-04) to XZ.

Author information

Conceptualization: X(xia)Z and XWB; methodology: XZ, WQD, LC, HML, JYM, MFC, JFX and XDL; formal analysis: XZ, X(xia)Z; resources: XHY, SCY, YFP, YHC, WJJ, YW, X(xia)Z and SQL; writing of original draft: XZ; manuscript review and editing: all authors; supervision: X(xia)Z, and XWB.

Correspondence to Xia Zhang or Xiu-wu Bian.

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Zhang, X., Chen, L., Dang, W. et al. CCL8 secreted by tumor-associated macrophages promotes invasion and stemness of glioblastoma cells via ERK1/2 signaling. Lab Invest (2019). https://doi.org/10.1038/s41374-019-0345-3

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