胶质瘤
恶性肿瘤
癌症研究
生物
肿瘤微环境
免疫系统
癌症干细胞
癌细胞
表型
重编程
渗透(HVAC)
癌症
免疫学
细胞
干细胞
细胞生物学
物理
基因
热力学
生物化学
遗传学
作者
Yuyang Liu,Ying Shi,Mengwan Wu,Jialin Liu,Hong Wu,Chuan Xu,Ling Chen
摘要
Polypoid giant cancer cells (PGCCs) represent a unique subgroup of stem-like cells, acting as a critical factor in promoting the recurrence of various solid tumors. The effect of PGCCs on the tumor malignancy of glioma and its immune microenvironment remains unclear.Bioinformatic analysis was performed to investigate the relationship between M2 tumor-associated macrophages (TAMs) infiltration and survival of glioblastoma (GBM) patients. The spatial location of M2 TAMs in GBM was also investigated using the Ivy Glioblastoma Atlas Project (Ivy GAP) database. PGCCs were quantified in glioma of different grades. CoCl2 was used to induce PGCCs in cultures of A172 cells. PGCCs, and their progeny cells in cultures were further evaluated for morphological features, tumorsphere formation, and TAMs activation.The magnitude of M2 TAMs infiltration is significantly correlated with poor survival in GBM patients. M2 TAMs were enriched in the perinecrotic zone (PNZ) of GBM and positively correlated with hypoxic levels. Increased PGCCs were detected in glioma specimens of higher grades. CoCl2 induced hypoxia and the transformation of A172 cultures into PGCCs, producing the progeny cells, PGCCs-Dau, through asymmetric division. PGCCs and PGCCs-Dau possessed tumor stem cell-like features, while PGCCs-Dau enhanced the polarization of TAMs into an M2 phenotype with relevance to immunosuppression and malignancy in GBM.PGCCs promote malignancy and immune-suppressive microenvironment in GBM. PGCCs or their progeny cells may be a potential therapeutic target for GBM.
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