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

By Wenchao Zhou, Susan Q. Ke, Zhi Huang, William A. Flavahan, X. Fang, J. Paul, Ling Wu, A. Sloan, R. McLendon, Xiaoxia Li and 2 more. Nature Cell Biology, 2015

839 citations recorded by the source corpus.

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.

Subfields: Immunology, Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/6c5b66ad1c47b1b8a704b4f641da15ff02bc61ad

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In Immunology

1. Jonathan M Cooper
2. J. Joyce
3. D. Quail
4. F. Giancotti

In Molecular Biology

1. Jonathan M Cooper
2. Jeremy N. Rich
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Citations in the corpus

• Integrin Signaling in Cancer: Mechanotransduction, Stemness, Epithelial Plasticity, and Therapeutic Resistance (2019, background): “In contrast, M2-like tumor-associated macrophages use the αvβ3 integrin to bind to periostin (POSTN) and home to the GBM stem cell niche (Zhou et al., 2015).”
• Cancer stem cells in glioblastoma (2015, background): “CSCs located at the perivascular niche are in close contact with the endothelial cells (Calabrese et al. 2007), permitting engagement of endothelial cell Notch ligands with glioma CSC Notch receptors to activate Notch signaling, which supports self-renewal of glioma CSCs (Zhu et al. 2011).”
• The microenvironmental landscape of brain tumors (2017, background): “, 2013), it is not surprising that activated TAMs have been shown to regulate glioma stem cell pools within the brain (Sarkar et al., 2014;Wu et al., 2010; Zhou et al., 2015).”