Extracellular ATP Reduces Tumor Sphere Growth and Cancer Stem Cell Population in Glioblastoma Cells

Overview

Journal Purinergic Signal

Publisher Springer

Date 2011 Aug 6

PMID 21818572

Citations 30

Authors

Pitia Flores Ledur

Emilly Schlee Villodre

Romela Paulus

Lavinia Almeida Cruz

Debora Gazzana Flores

Guido Lenz

Affiliations

Soon will be listed here.

Abstract

Glioblastoma is the most aggressive tumor in the CNS and is characterized by having a cancer stem cell (CSC) subpopulation essential for tumor survival. The purinergic system plays an important role in glioma growth, since adenosine triphosphate (ATP) can induce proliferation of glioma cells, and alteration in extracellular ATP degradation by the use of exogenous nucleotidases dramatically alters the size of gliomas in rats. The aim of this work was to characterize the effect of the purinergic system on glioma CSCs. Human U87 glioma cultures presented tumor spheres that express the markers of glioma cancer stem cells CD133, Oct-4, and Nanog. Messenger RNA of several purinergic receptors were differently expressed in spheres when compared to a cell monolayer not containing spheres. Treatment of human gliomas U87 or U343 as well as rat C6 gliomas with 100 μM of ATP reduced the number of tumor spheres when grown in neural stem cell medium supplemented with epidermal growth factor and basic fibroblast growth factor. Moreover, ATP caused a decline in the number of spheres observed in culture in a dose-dependent manner. ATP also reduces the expression of Nanog, as determined by flow cytometry, as well as CD133 and Oct-4, as analyzed by flow cytometry and RT-PCR in U87 cells. The differential expression of purinergic receptor in tumor spheres when compared to adherent cells and the effect of ATP in reducing tumor spheres suggest that the purinergic system affects CSC biology and that ATP may be a potential agonist for differentiation therapy.

Citing Articles

Purinergic system in cancer stem cells.

Nunez-Rios J, Ulrich H, Diaz-Munoz M, Lameu C, Vazquez-Cuevas F Purinergic Signal. 2023; 21(1):23-38.

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Purinergic Signaling and its Role in the Stem Cell Differentiation.

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Purinergic signaling: Diverse effects and therapeutic potential in cancer.

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A Adenosine Receptor Enhances Chemoresistance of Glioblastoma Stem-Like Cells under Hypoxia: New Insights into MRP3 Transporter Function.

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Extracellular ATP and Macropinocytosis: Their Interactive and Mutually Supportive Roles in Cell Growth, Drug Resistance, and EMT in Cancer.

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