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Updated: Jul 17, 2025

Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion
Published on: October 20, 2016
Tumor-associated monocytes promote mesenchymal transformation through EGFR signaling in glioma
Yiyun Chen1, Ran Huo2, Weirong Kang3
1Division of Life Science, Department of Chemical and Biological Engineering, and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong SAR, China; SIAT-HKUST Joint Laboratory of Cell Evolution and Digital Health, HKUST Shenzhen-Hong Kong Collaborative Innovation Research Institute, Futian, Shenzhen, China.
Abstract:
The role of brain immune compartments in glioma evolution remains elusive. We profile immune cells in glioma microenvironment and the matched peripheral blood from 11 patients. Glioblastoma exhibits specific infiltration of blood-originated monocytes expressing epidermal growth factor receptor (EGFR) ligands EREG and AREG, coined as tumor-associated monocytes (TAMo). TAMo infiltration is mutually exclusive with EGFR alterations (p = 0.019), while co-occurring with mesenchymal subtype (p = 4.7 × 10-7) and marking worse prognosis (p = 0.004 and 0.032 in two cohorts). Evolutionary analysis of initial-recurrent glioma pairs and single-cell study of a multi-centric glioblastoma reveal association between elevated TAMo and glioma mesenchymal transformation. Further analyses identify FOSL2 as a TAMo master regulator and demonstrates that FOSL2-EREG/AREG-EGFR signaling axis promotes glioma invasion in vitro. Collectively, we identify TAMo in tumor microenvironment and reveal its driving role in activating EGFR signaling to shape glioma evolution.
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