Tumour-associated macrophages secrete pleiotrophin to promote PTPRZ1 signalling in glioblastoma stem cells for tumour growth

Yu Shi, Yi-Fang Ping, Wenchao Zhou, Zhi-Cheng He, Cong Chen, Bai-Shi-Jiao Bian, Lin Zhang, Lu Chen, Xun Lan, Xian-Chao Zhang, Kai Zhou, Qing Liu, Hua Long, Ti-Wei Fu, Xiao-Ning Zhang, Mian-Fu Cao, Zhi Huang, Xiaoguang Fang, Xiuxing Wang, Hua Feng, Xiao-Hong Yao, Shi-Cang Yu, You-Hong Cui, Xia Zhang, Jeremy N Rich, Shideng Bao () and Xiu-Wu Bian ()
Additional contact information
Yu Shi: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, The Third Military Medical University
Yi-Fang Ping: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, The Third Military Medical University
Wenchao Zhou: Lerner Research Institute, Cleveland Clinic
Zhi-Cheng He: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, The Third Military Medical University
Cong Chen: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, The Third Military Medical University
Bai-Shi-Jiao Bian: Southwest Hospital, The Third Military Medical University
Lin Zhang: Xijing Hospital, The Fourth Military Medical University
Lu Chen: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, The Third Military Medical University
Xun Lan: Stanford University
Xian-Chao Zhang: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, The Third Military Medical University
Kai Zhou: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, The Third Military Medical University
Qing Liu: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, The Third Military Medical University
Hua Long: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, The Third Military Medical University
Ti-Wei Fu: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, The Third Military Medical University
Xiao-Ning Zhang: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, The Third Military Medical University
Mian-Fu Cao: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, The Third Military Medical University
Zhi Huang: Lerner Research Institute, Cleveland Clinic
Xiaoguang Fang: Lerner Research Institute, Cleveland Clinic
Xiuxing Wang: Lerner Research Institute, Cleveland Clinic
Hua Feng: Southwest Hospital, The Third Military Medical University
Xiao-Hong Yao: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, The Third Military Medical University
Shi-Cang Yu: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, The Third Military Medical University
You-Hong Cui: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, The Third Military Medical University
Xia Zhang: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, The Third Military Medical University
Jeremy N Rich: Lerner Research Institute, Cleveland Clinic
Shideng Bao: Lerner Research Institute, Cleveland Clinic
Xiu-Wu Bian: Institute of Pathology and Southwest Cancer Centre, Southwest Hospital, The Third Military Medical University

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: Abstract Intense infiltration of tumour-associated macrophages (TAMs) facilitates malignant growth of glioblastoma (GBM), but the underlying mechanisms remain undefined. Herein, we report that TAMs secrete abundant pleiotrophin (PTN) to stimulate glioma stem cells (GSCs) through its receptor PTPRZ1 thus promoting GBM malignant growth through PTN–PTPRZ1 paracrine signalling. PTN expression correlates with infiltration of CD11b+/CD163+ TAMs and poor prognosis of GBM patients. Co-implantation of M2-like macrophages (MLCs) promoted GSC-driven tumour growth, but silencing PTN expression in MLCs mitigated their pro-tumorigenic activity. The PTN receptor PTPRZ1 is preferentially expressed in GSCs and also predicts GBM poor prognosis. Disrupting PTPRZ1 abrogated GSC maintenance and tumorigenic potential. Moreover, blocking the PTN–PTPRZ1 signalling by shRNA or anti-PTPRZ1 antibody potently suppressed GBM tumour growth and prolonged animal survival. Our study uncovered a critical molecular crosstalk between TAMs and GSCs through the PTN–PTPRZ1 paracrine signalling to support GBM malignant growth, indicating that targeting this signalling axis may have therapeutic potential.

Date: 2017
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DOI: 10.1038/ncomms15080

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