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posted on 2023-03-31, 02:05 authored by Zhenyi An, Christiane B. Knobbe-Thomsen, Xiaohua Wan, Qi Wen Fan, Guido Reifenberger, William A. Weiss Western blotting of IκB and p-IκB from protein lysates of U87 cells expressing EGFR, EGFRvIII, or both genes.
Funding
Alex's Lemonade Stand Foundation
American Brain Tumor Association
NIH
Sandler Foundation
German Cancer Aid
BMBF
Samuel Waxman Cancer Research Foundation
History
ARTICLE ABSTRACT
Amplification of the EGFR gene and its truncation mutant EGFRvIII are hallmarks of glioblastoma. Although coexpression of EGFR and EGFRvIII confers a growth advantage, how EGFR and EGFRvIII influence the tumor microenvironment remains incompletely understood. Here, we show that EGFR and EGFRvIII cooperate to induce macrophage infiltration via upregulation of the chemokine CCL2. EGFRvIII was significantly enriched in glioblastoma patient samples with high CCL2, and knockout of CCL2 in tumors coexpressing EGFR and EGFRvIII led to decreased infiltration of macrophages. KRAS was a critical signaling intermediate for EGFR- and EGFRvIII-induced expression of CCL2. Our results illustrate how EGFR and EGFRvIII direct the microenvironment in glioblastoma.
Full-length EGFR and truncated EGFRvIII work through KRAS to upregulate the chemokine CCL2 and drive macrophage infiltration in glioblastoma.
