Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
Lab Invest. 2020 Apr;100(4):619-629. doi: 10.1038/s41374-019-0345-3. Epub 2019 Nov 20.
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（TAMs）构成了胶质母细胞瘤的一个大群体，促进了肿瘤的生长和肿瘤细胞的侵袭，但潜在的机制仍未确定。在这项研究中，我们证明趋化因子（C-C 基序）配体 8（CCL8）在 TAMs 中高度表达，并有助于 GBM 细胞形成伪足。CCL8 存在于神经胶质瘤微环境中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 显著激活 GBM 细胞中 ERK1/2 的磷酸化，用中和抗体阻断 TAM 分泌的 CCL8 可显著降低神经胶质瘤细胞的侵袭。综上所述，我们的数据表明 CCL8 是一种与 TAMs 相关的因子，可介导 GBM 的侵袭和干细胞样特征，靶向 CCL8 可能为 GBM 的治疗提供一种新策略。
