EGFR Cooperates with EGFRvIII to Recruit Macrophages in Glioblastoma

被引：54

作者：

An, Zhenyi ^{[1
]}

Knobbe-Thomsen, Christiane B. ^{[2
]}

Wan, Xiaohua ^{[1
]}

Fan, Qi Wen ^{[1
]}

Reifenberger, Guido ^{[2
]}

Weiss, William A. ^{[1
,3
,4
,5
]}

机构：

[1] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA

[2] Heinrich Heine Univ, Dept Neuropathol, Dusseldorf, Germany

[3] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA

[5] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA

来源：

CANCER RESEARCH | 2018年 / 78卷 / 24期

关键词：

POLARIZATION; INFILTRATION; EXPRESSION; DRIVEN; CELL;

D O I：

10.1158/0008-5472.CAN-17-3551

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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. Significance: Full-length EGFR and truncated EGFRvIII work through KRAS to upregulate the chemokine CCL2 and drive macrophage infiltration in glioblastoma. (C) 2018 AACR.

引用

页码：6785 / 6794

页数：10

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