Periostin Secreted by Glioblastoma Stem Cells Recruits M2 Tumour-associated Macrophages and Promotes Malignant Growth

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2015 Jan 13

PMID 25580734

Citations 491

Authors

Wenchao Zhou

Susan Q Ke

Zhi Huang

William Flavahan

Xiaoguang Fang

Jeremy Paul

Ling Wu

Andrew E Sloan

Roger E McLendon

Xiaoxia Li

Jeremy N Rich

Shideng Bao

Affiliations

Soon will be listed here.

Abstract

Tumour-associated macrophages (TAMs) are enriched in glioblastoma multiformes (GBMs) that contain glioma stem cells (GSCs) at the apex of their cellular hierarchy. The correlation between TAM density and glioma grade suggests a supportive role for TAMs in tumour progression. Here we interrogated the molecular link between GSCs and TAM recruitment in GBMs and demonstrated that GSCs secrete periostin (POSTN) to recruit TAMs. TAM density correlates with POSTN levels in human GBMs. Silencing POSTN in GSCs markedly reduced TAM density, inhibited tumour growth, and increased survival of mice bearing GSC-derived xenografts. We found that TAMs in GBMs are not brain-resident microglia, but mainly monocyte-derived macrophages from peripheral blood. Disrupting POSTN specifically attenuated the tumour-supportive M2 type of TAMs in xenografts. POSTN recruits TAMs through the integrin αvβ₃ as blocking this signalling by an RGD peptide inhibited TAM recruitment. Our findings highlight the possibility of improving GBM treatment by targeting POSTN-mediated TAM recruitment.

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