title: The expression of P2X₇ receptors in EPCs and their potential role in the targeting of EPCs to brain gliomas.
abstract: In order to use endothelial progenitor cells (EPCs) as a therapeutic and imaging probe to overcome antiangiogenic resistance for gliomas, how to enhance proliferation and targeting ability of transplanted EPCs is a high priority. Here, we confirmed, for the first time, the expression of P2X7 receptors in rat spleen-derived EPCs. Activation of P2X7 receptors in EPCs by BzATP promoted cells proliferation and migration, rather than apoptosis. In vivo, the homing of transplanted EPCs after long-term suppression of P2X7 receptors by persistent BBG stimulation was evaluated by MRI, immunohistochemistry and flow cytometry. Compared to the group without BBG treatment, less transplanted EPCs homed to gliomas in the group with BBG treatment, especially integrated into the vessels containing tumor-derived endothelial cells in gliomas. Moreover, western blot showed that CXCL1 expression was downregulated in gliomas with BBG treatment, which meant P2X7 receptors suppression inhibited the homing of EPCs to gliomas through down-regulation of CXCLl expression. Further, effects of P2X7 receptors on C6 glioma cells or gliomas were evaluated at the same dose of BzATP or BBG used in EPCs experiments in vitro and in vivo. MTT assay and MRI revealed that P2X7 receptors exerted no significant promoting effect on C6 glioma cells proliferation, gliomas growth and angiogenesis. Taken together, our findings imply the possibility of promoting proliferation and targeting ability of transplanted EPCs to brain gliomas in vivo through P2X7 receptors, which may provide new perspectives on application of EPCs as a therapeutic and imaging probe to overcome antiangiogenic resistance for gliomas.
authors.affiliation: a Department of Radiology; Institute of Surgery Research; Daping Hospital; Third Military Medical University ; Chongqing , China.
authors.forename: Jingqin
authors.initials: J
authors.lastname: Fang
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Shunan
authors.initials: S
authors.lastname: Wang
authors.forename: Tian
authors.initials: T
authors.lastname: Xie
authors.forename: Xuesong
authors.initials: X
authors.lastname: Du
authors.forename: Heng
authors.initials: H
authors.lastname: Liu
authors.forename: Sumei
authors.initials: S
authors.lastname: Wang
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.forename: Jinhua
authors.initials: J
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Huaping
authors.initials: H
authors.lastname: Liang
authors.forename: Yizeng
authors.initials: Y
authors.lastname: Yang
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D054360:Chemokine CXCL1 / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D005910:Glioma / Q000235:genetics*; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000235:genetics*
chemical_list: C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; C546468:P2RX7 protein, human; D058486:Receptors, Purinergic P2X7
keywords: C6 glioma cells; DCE, dynamic contrast enhanced; ECs, endothelial cells; EPCs, endothelial progenitor cells; GSCs, glioma stem-like cells; HSCs, hematopoietic stem cells; MRI, magnetic resonance imaging; P2X7 receptors; SDF-1α, Stromal derived factor 1α; VEGF, vascular endothelial growth factor; endothelial progenitor cells; glioma; magnetic resonance imaging
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