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

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 prom... Full description

Journal Title: Nature Communications 2017, Vol.8
Main Author: Yu Shi
Other Authors: 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 , Xiu-Wu Bian
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ID: ISSN: 2041-1723 ; E-ISSN: 2041-1723 ; DOI: 10.1038/ncomms15080
Link: http://dx.doi.org/10.1038/ncomms15080
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recordid: nature_a10.1038/ncomms15080
title: Tumour-associated macrophages secrete pleiotrophin to promote PTPRZ1 signalling in glioblastoma stem cells for tumour growth
format: Article
creator:
  • 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
  • Xiu-Wu Bian
subjects:
  • Biology
ispartof: Nature Communications, 2017, Vol.8
description: 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.
language:
source:
identifier: ISSN: 2041-1723 ; E-ISSN: 2041-1723 ; DOI: 10.1038/ncomms15080
fulltext: fulltext
issn:
  • 2041-1723
  • 20411723
url: Link


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titleTumour-associated macrophages secrete pleiotrophin to promote PTPRZ1 signalling in glioblastoma stem cells for tumour growth
creatorYu 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 ; Xiu-Wu Bian
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descriptionIntense 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.
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titleTumour-associated macrophages secrete pleiotrophin to promote PTPRZ1 signalling in glioblastoma stem cells for tumour growth
authorYu 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 ; Xiu-Wu Bian
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