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CD47 promotes the proliferation and migration of adamantinomatous craniopharyngioma cells by activating the MAPK/ERK pathway, and CD47 blockade facilitates microglia‐mediated phagocytosis

CD47型 吞噬作用 MAPK/ERK通路 小胶质细胞 细胞生物学 体外 生物 流式细胞术 免疫系统 癌症研究 分子生物学 免疫学 炎症 信号转导 生物化学
作者
Huarong Zhang,Chaohu Wang,Jun Fan,Qianchao Zhu,Yiwen Feng,Jun Pan,Junxiang Peng,Shi Jin,Songtao Qi,Yi Liu
出处
期刊:Neuropathology and Applied Neurobiology [Wiley]
卷期号:48 (4) 被引量:15
标识
DOI:10.1111/nan.12795
摘要

CD47 is overexpressed in multiple tumours and plays an important role in immune escape and other biological processes of tumours. However, its role in adamantinomatous craniopharyngioma (ACP) remains unclear. Therefore, we explored the functions of CD47 in ACP.In this study, the expression of CD47 and the infiltration of immune cells in ACP was determined by immunohistochemistry (IHC) or immunofluorescence. Microglia-mediated phagocytosis was analysed using an in vitro phagocytosis assay. Using lentivirus transfection, CD47 was either silenced or overexpressed in primary ACP cells and the biological effects of CD47 on these cells were evaluated in vitro using cell viability, flow cytometry, wound healing, Transwell migration and 3D hydrogel assays. The protein expression levels were analysed by western blotting.Finger-like protrusions, which may be the key factor in the recurrence of ACP, were primarily found in the region of hypothalamic involvement. The expression of CD47 was higher in palisading epithelium compared with stellate reticulum and epithelial whorls. An in vitro phagocytosis assay showed that CD47 blockade could promote microglia-mediated phagocytosis. Functional assays revealed that CD47 promoted the growth, migration and invasion of ACP cells in vitro. Our mechanistic investigations showed that CD47 activated the MAPK/ERK pathway, thereby facilitating the biological behaviour of ACP cells.Here, we demonstrated that CD47 plays an important role in ACP cells, suggesting that CD47 could be a new potential therapeutic target for ACP, and adding to the body of literature a role for the inhibition of MAPK/ERK in ACP.
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