CCL8 secreted by tumor-associated macrophages promotes invasion and stemness of glioblastoma cells via ERK1/2 signaling.
Xiang ZhangLu ChenWei-Qi DangMian-Fu CaoJing-Fang XiaoSheng-Qing LvWen-Jie JiangXiao-Hong YaoHui-Min LuJing-Ya MiaoYan WangShi-Cang YuYi-Fang PingXin-Dong LiuYou-Hong CuiXia ZhangXiu-Wu BianPublished in: Laboratory investigation; a journal of technical methods and pathology (2019)
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.
Keyphrases
- liver fibrosis
- liver injury
- induced apoptosis
- drug induced
- cell cycle arrest
- cell migration
- stem cells
- signaling pathway
- pi k akt
- cell proliferation
- epithelial mesenchymal transition
- endoplasmic reticulum stress
- gene expression
- machine learning
- regulatory t cells
- drug delivery
- electronic health record
- single cell
- stress induced
- data analysis