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Purinergic Signaling in Glioma Progression

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Glioma Signaling

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 986))

Abstract

Among the pathological alterations that give tumor cells invasive potential, purinergic signaling is emerging as an important component. Studies performed in in vitro, in vivo and ex vivo glioma models indicate that alterations in the purinergic signaling are involved in the progression of these tumors. Gliomas have low expression of all E-NTPDases, when compared to astrocytes in culture. Nucleotides induce glioma proliferation and ATP, although potentially neurotoxic, does not evoke cytotoxic action on the majority of glioma cells in culture. The importance of extracellular ATP for glioma pathobiology was confirmed by the reduction in glioma tumor size by apyrase, which degrades extracellular ATP to AMP, and the striking increase in tumor size by over-expression of an ecto-enzyme that degrades ATP to ADP, suggesting the effect of extracellular ATP on the tumor growth depends on the nucleotide produced by its degradation. The participation of purinergic receptors on glioma progression, particularly P2X7, is involved in the resistance to ATP-induced cell death. Although more studies are necessary, the purinergic signaling, including ectonucleotidases and receptors, may be considered as future target for glioma pharmacological or gene therapy.

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Abbreviations

ADA:

Adenosine deaminase

ADP:

Adenosine diphosphate

Akt:

Protein kinase B

ALP:

Alkaline phosphatase

AMP:

Adenosine monophosphate

APCP:

α,β-Methylene ADP

Apyrase:

Adenyl-pyrophosphatase

ATP:

Adenosine triphosphate

BBB:

Brain blood barrier

BBG:

Brilliant Blue G

BzATP:

2,3-(Benzoyl-4-benzoyl)-ATP

CDK:

Cyclin-dependent kinase

CDKN2A (Ink4a/ARF):

Cyclin-dependent kinase inhibitor 2A

CSCs:

Cancer stem cell

ECM:

Extracellular matrix

Ecto-5′-NT/CD73:

Ecto-5′-nucleotidase

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

E-NPP:

Ectonucleoside pyrophosphatase/phosphodiesterase

E-NTPDase:

Ectonucleoside triphosphate diphosphohydrolase

ERBB2:

Human epidermal growth factor receptor 2

ERK:

Extracellular signal-regulated kinases

FGF:

Fibroblast growth factor

IL-1β:

Interleukin 1β

IL-6:

Interleukin 6

KO:

Knockout

MDM2:

Murine double minute 2

MET:

NF1, neurofibromatosis 1

MMP-9:

Metalloproteinase-9

NPCs:

Neural precursor cell

NSC:

Neural stem cell

OPC:

Oligodendrocyte precursor cell

PDGF:

Platelet-derived growth factor

PI3K:

Phosphatidylinositol 3-kinase

PTEN:

Phosphatase and tensin homolog

Ras/MAPK:

Ras/Mitogen activated protein kinase

Ras-GAP:

Ras-GTPase activating protein

NF1:

Neurofibrimatosis 1

RB1:

Retinoblastoma

CNS:

Central nervous system

SVZ:

Subventricular zone

TNF-α:

Tumor necrosis factor

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Acknowledgments

We thank Dr. Maria Isabel A. Edelweiss, Departamento de Patologia, HCPA, UFRGS; Fernanda B. Morrone, Faculdade de Farmácia, PUCRS, Porto Alegre, RS, Brasil; Dr. Simon C. Robson, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA and Dr. Jean Sevigny, Centre de Recherche en Rheumatologie et Immunologie, Centre Hospitalier Universitaire de Québec (Pavillon CHUL) and Département de Microbiologie-Infectiologie et d’Immunologie, Faculté de Médecine, Université Laval, Québec, QC, Canada, for their collaboration. We thank the BioMed Central and Willey Editors for the Copyright permission of Figs. 5.1 and 5.2, published in the papers Morrone et al. (2006) (BMC Cancer 23:226) and Braganhol et al. (2009) (Cancer Sci 100(8): 1434–1442), respectively. We also acknowledge the Brazilian Funding Agencies: CNPq, CAPES, FIPE-HCPA and FAPERGS for the financial support.

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  1. Centro de Ciências Químicas, Farmacêuticas e de Alimentos (CCQFA), Universidade Federal de Pelotas (UFPel), Campus Capão do Leão S/N, 354, Pelotas, CEP 96010900, RS, Brazil

    Elizandra Braganhol

  2. Departamento de Ciências Básicas da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, 245 Rua Sarmento Leite, Porto Alegre, CEP 90050-170, RS, Brazil

    Márcia Rosângela Wink

  3. Departamento de Biofísica, IB e Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, 9500 Av. Bento Goncalves, Porto Alegre, 61501970, RS, Brazil

    Guido Lenz

  4. Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, 2600-anexo Rua Ramiro Barcelos, Porto Alegre, CEP 90035-003, RS, Brazil

    Ana Maria Oliveira Battastini

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  1. Elizandra Braganhol
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Correspondence to Elizandra Braganhol .

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  1. , Biochemistry, Nencki Institute of Experimental Biology, Pasteur 3, Warsaw, 02-093, Poland

    Jolanta Barańska

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Braganhol, E., Wink, M.R., Lenz, G., Battastini, A.M.O. (2013). Purinergic Signaling in Glioma Progression. In: Barańska, J. (eds) Glioma Signaling. Advances in Experimental Medicine and Biology, vol 986. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4719-7_5

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