Periostin secreted by glioblastoma stem cells recruits M2 tumour-associated macrophages and promotes malignant growth.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zhou, W; Ke, SQ; Huang, Z; Flavahan, W; Fang, X; Paul, J; Wu, L; Sloan, AE; McLendon, RE; Li, X; Rich, JN; Bao, S

Published Date

  • February 2015

Published In

Volume / Issue

  • 17 / 2

Start / End Page

  • 170 - 182

PubMed ID

  • 25580734

Pubmed Central ID

  • 25580734

Electronic International Standard Serial Number (EISSN)

  • 1476-4679

International Standard Serial Number (ISSN)

  • 1465-7392

Digital Object Identifier (DOI)

  • 10.1038/ncb3090

Language

  • eng