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.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81230062, 61327902-4]; National Key Research and Development Program of China [2016YFA0101203]; Key Laboratory of Tumour Immunology and Pathology [2015jsz101]; National Postdoctoral Program for Innovative Talents [BX201600024]; Southwest Hospital Innovation Program [SWH2016JCYB-15]; NIH (USA) R01 grants [CA184090, NS091080, NS099175]
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外文
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最新[2023]版：
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第一作者：
第一作者机构：[1]Third Mil Med Univ, Inst Pathol, Chongqing 400038, Peoples R China;[2]Third Mil Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing 400038, Peoples R China;[3]Minist Educ China, Key Lab Tumour Immunopathol, Chongqing 400038, Peoples R China;
通讯作者：
通讯机构：[1]Third Mil Med Univ, Inst Pathol, Chongqing 400038, Peoples R China;[2]Third Mil Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing 400038, Peoples R China;[3]Minist Educ China, Key Lab Tumour Immunopathol, Chongqing 400038, Peoples R China;[4]Cleveland Clin, Lerner Res Inst, Dept Stem Cell Biol & Regenerat Med, Cleveland, OH 44195 USA;[9]Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Guangzhou 510095, Guangdong, Peoples R China
推荐引用方式(GB/T 7714)：
Shi Yu,Ping Yi-Fang,Zhou Wenchao,et al.Tumour-associated macrophages secrete pleiotrophin to promote PTPRZ1 signalling in glioblastoma stem cells for tumour growth[J].Nature communications.2017,8:-.doi:10.1038/ncomms15080.
APA：
Shi, Yu,Ping, Yi-Fang,Zhou, Wenchao,He, Zhi-Cheng,Chen, Cong...&Bian, Xiu-Wu.(2017).Tumour-associated macrophages secrete pleiotrophin to promote PTPRZ1 signalling in glioblastoma stem cells for tumour growth.Nature communications,8,
MLA：
Shi, Yu,et al."Tumour-associated macrophages secrete pleiotrophin to promote PTPRZ1 signalling in glioblastoma stem cells for tumour growth".Nature communications 8.(2017):-
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