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

 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 and Shideng Bao

Nature cell biology, 2015

Speaker: Dong-Jer Shiau (蕭東哲)                               Time: 13:10~14:00, Apr. 15, 2015

Commentator: Dr. Yan-Shen Shan (沈延盛 醫師)       Place: Room 601

Abstract:

Glioblastoma multiforme (GBM) is the one of the most aggressive forms of glioma. Currently employed therapies, including surgery, radiation and chemotherapy were not satisfied. Tumor-associated macrophage (TAM) infiltration has been reported in GBM prognosis. TAM can promote GBM neo-vascularization and escape from immune surveillance _[1]. Therefore, TAM plays an important role to support GBM progression. However, the mechanism of TAM recruitment by GBM is still unclear. It is suggested that glioblastoma stem cells (GSCs) contributes to GBM tumor growth, vascularization and chemo-drug resistance _[2]. Furthermore, GSCs are localized in GBM niches which also contains more population of TAM. Therefore, authors would like to investigate the factors secreted from GSC in recruiting the TAM. Initially, the authors have analyzed different kinds of secreting factors which are produced by GSCs. Bioinformatic analysis results have indicated that periostin (POSTN) is the most potent protein expressed in GSCs. Later on, they have found that silencing POSTN in GSCs decreases TAM density and tumor growth in xenograft. In addition, the transwell migration and invasion assay indicate that silencing of POSTN in GSCs reduces TAM recruitment. In the other hand, the authors have further determined underlying mechanism by recruitment of TAM POSTN. Previous researches have shown that POSTN is involved in integrin α_vβ₃ signaling. Therefore, the authors further employed integrin inhibitory peptide (RGD) to determine TAM recruitment via integrin signaling. Results have shown that RGD could reduce TAM recruitment, mice tumor growth and GBM-bearing mice mortality. In conclusion, GSC could secrete POSTN to recruit TAM from blood vessels via triggering integrin α_vβ₃ signaling. Integrin inhibitory peptide (RGD) might synergize with immunotherapy for patients with GBM and other cancers to increase the efficacy of the treatment.

References:

1.         Hirano, H., et al. Angiogenic effect of thymidine phosphorylase on macrophages in glioblastoma multiforme. Journal of Neurosurgery, 2001, 89-95

2.         Du, R., et al. HIF1α induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell, 2008, 206-220