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Adenosine Signaling in Glioma Cells

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Glioma Signaling

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

Abstract

Purines and pyrimidines are fundamental signaling molecules in controlling the survival and proliferation of astrocytes, as well as in mediating cell-to-cell communication between glial cells and neurons in the healthy brain. The malignant transformation of astrocytes towards progressively more aggressive brain tumors (from astrocytoma to anaplastic glioblastoma) leads to modifications in both the survival and cell death pathways which overall confer a growth advantage to malignant cells and resistance to many cytotoxic stimuli. It has been demonstrated, however, that, in astrocytomas, several purinergic (in particular adenosinergic) pathways controlling cell survival and death are still effective and, in some cases, even enhanced, providing invaluable targets for purine-based chemotherapy, that still represents an appropriate pharmacological approach to brain tumors. In this chapter, the current knowledge on both receptor-mediated and receptor-independent adenosine pathways in astrocytomas will be reviewed, with a particular emphasis on the most promising targets which could be translated from in vitro studies to in vivo pharmacology.

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Abbreviations

ADA:

Adenosine deaminase

Ado:

Adenosine

AK:

Adenosine kinase

APCP:

α,β-Methylene ADP

2-CA:

2-Chloro-adenosine

2-CdA:

2-Chloro-2′-deoxyadenosine

CI-IB-MECA:

2-Chloro-N6-(3-iodobenzyl)-N-methyl-5′-carbamoyladenosine

CNS:

Central Nervous System

8-CPT:

8-Cyclo-pentyl-theophylline

DAG:

Diacylglycerol

dCyd:

2′-Deoxycytidine

ENT:

Equilibrative nucleoside transporter

18F-CPFPX:

8-Cyclopentyl-3-(3-18F-fluoropropyl)-1-propyl-xanthine

GSK-3β:

Glycogen synthase kinase 3β

HIF-1α:

Hypoxia-inducible factor 1 α subunit

IFNγ:

Interferon-gamma

Ino:

Inosine

IP3 :

Inositol-1,4,5-trisphosphate

ITub:

5-Iodotubercidin

MAP kinases:

Mitogen-activated protein kinases

MMP-9:

Matrix metalloproteinase-9

MRS1220:

N-(9-Chloro-2-furan-2-yl-[1,2,4]triazolo[1,5-c]quinazolin-5-yl)-2-phenylacetamide

MRS1706:

N-(4-Acetylphenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)phenoxy] acetamide

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NECA:

N-Ethyl-carboxamide adenosine

NTPDase:

Nucleoside triphosphate diphosphohydrolase

PET:

Positron emission tomography

PI:

Propidium iodide

PI3K:

Phosphatidylinositol 3-kinase

PKA:

Protein kinase A

PKB/Akt:

Protein kinase B

PKC:

Protein kinase C

PLC:

Phospholipase C

PLD:

Phospholipase D

SAH:

S-Adenosyl-homocysteine

SAM:

S-Adenosyl-methionine

TNFα:

Tumour necrosis factor alpha

VEGF:

Vascular endothelial growth factor

zIETD-fmk:

z-Ile-Glu(OMe)-Thr-Asp(OMe)-fluoromethylketone

zLEHD-fmk:

z-Leu-Glu(OMe)-His-Asp(OMe)-fluoromethylketone

zVAD-fmk:

z-Val-Ala-Asp(OMe)-fluoromethylketone

zVDVAD-fmk:

z-Val-Asp(OMe)-Val-Ala-Asp(OMe)-fluoromethylketone.

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Authors and Affiliations

  1. Laboratory of Molecular and Cellular Pharmacology of Purinergic Transmission, Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 9 via Balzaretti, 20133, Milan, Italy

    Stefania Ceruti & Maria P. Abbracchio

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  1. Stefania Ceruti
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  2. Maria P. Abbracchio
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Correspondence to Stefania Ceruti .

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

    Jolanta Barańska

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Ceruti, S., Abbracchio, M.P. (2013). Adenosine Signaling in Glioma Cells. 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_2

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