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.

肿瘤相关巨噬细胞 (TAM) 构成大量胶质母细胞瘤并促进肿瘤生长和肿瘤细胞侵袭，但其潜在机制仍未明确。在这项研究中，我们证明趋化因子（CC 基序）配体 8 (CCL8) 由 TAM 高表达，并有助于 GBM 细胞形成伪足。CCL8 在神经胶质瘤微环境中的存在促进了肿瘤细胞的进展。此外，CCL8诱导GBM细胞的侵袭和干细胞样特征，CCR1和CCR5是介导CCL8诱导的生物学行为的主要受体。最后，CCL8 显着激活 GBM 细胞中的 ERK1/2 磷酸化，并且通过中和抗体阻断 TAM 分泌的 CCL8 显着减少神经胶质瘤细胞的侵袭。综合起来，