Dual role of ARPC1B in regulating the network between tumor-associated macrophages and tumor cells in glioblastoma.
Dual role of ARPC1B in regulating the network between tumor-associated macrophages and tumor cells in glioblastoma.
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ARPC1B 在调节胶质母细胞瘤中肿瘤相关巨噬细胞和肿瘤细胞之间网络的双重作用
DOI：
10.1080/2162402x.2022.2031499
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发表时间：
2022
期刊：
影响因子：
7.2
通讯作者：
Wu A
中科院分区：
文献类型：
--
作者：
Liu T;Zhu C;Chen X;Wu J;Guan G;Zou C;Shen S;Chen L;Cheng P;Cheng W;Wu A
肿瘤微环境（TME）在胶质母细胞瘤（GBM）的生长和转移中起着重要作用。肿瘤相关巨噬细胞（TAM）是浸润TME的最丰富的髓样细胞，产生促炎细胞因子，调节胶质瘤细胞库，并导致GBM进展。了解GBM-TAMs的调控机制有助于寻找新的针对GBM的靶向治疗策略。基于CGGA和TCGA GBM队列，ARPC 1B被定义为具有预后价值的关键巨噬细胞相关基因。ARPC 1B高表达与进展性恶性肿瘤、不良预后和TAM浸润相关。我们证明巨噬细胞表达的ARPC 1B促进胶质瘤细胞的迁移、侵袭和上皮-间质转化。胶质瘤内源性ARPC 1B也维持恶性表型并促进巨噬细胞募集。巨噬细胞和胶质瘤细胞之间通过ARPC 1B的正反馈信号被确定为在IFNγ-IRF 2-ARPC 1B轴的控制下。这项研究强调了ARPC 1B在GBM恶性进展中的重要作用以及GBM和TAM之间的调节网络，表明ARPC 1B是一种具有潜在治疗意义的新生物标志物。
ABSTRACT The tumor microenvironment (TME) plays a critical role in promoting the growth and metastasis of glioblastoma (GBM). Tumor-associated macrophages (TAMs), the most abundant myeloid cells infiltrating in TME, produce proinflammatory cytokines, regulate glioma cell pools, and lead to GBM progression. Understanding the mechanism of GBM-TAMs regulation can help to find new targeted therapeutic strategies against GBM. Based on the CGGA and TCGA GBM cohorts, ARPC1B was defined as the key macrophage-associated gene with prognostic value. Higher ARPC1B expression was associated with progressive malignancy, poor outcomes and TAM infiltration. We demonstrated that macrophage-expressed ARPC1B promoted the migration, invasion, and epithelial–mesenchymal transition of glioma cells. Glioma-intrinsic ARPC1B also maintained the malignant phenotype and promoted macrophage recruitment. Positive feedback signaling between macrophages and glioma cells via ARPC1B was determined to be under control of the IFNγ-IRF2-ARPC1B axis. This study highlights the important role of ARPC1B in GBM malignancy progression and the regulation network between GBM and TAMs, suggesting ARPC1B as a novel biomarker with potential therapeutic implications.