Glioma Signaling (eBook)

1. INTRODUCTION TO PURINERGIC SIGNALING IN THE BRAINGeoffrey BurnstockAbstract1.1 Introduction1.2 Purinergic Signalling in the CNS1.2.1 Cotransmission1.2.2 Glial Cells1.2.3 Neuron-Glial Interactions1.3 Purinergic Signalling in Normal Behaviour1.4 Purinergic Pathophysiology in the CNS, including GliomasReferences2. ADENOSINE SIGNALING IN GLIOMA CELLSStefania Ceruti and Maria P. AbbracchioAbstract2.1 Introduction2.2 Adenosine Metabolism and P1 Adenosine Receptors2.3 A Role for Ecto-5’-Nucleotidases CD39 and CD73 in Gliomas?2.4 Receptor-Mediated Effects of Adenosine on Glioma Cell Growth and Survival2.4.1 A1-, A2A-, and A2B-Mediated Effects on Glioma Cells2.4.2 The A3 Receptor Subtype as a New Pharmacological Ttarget for Innovative Chemotherapic Approaches to Gliomas2.5 Receptor-Idependent Effects of Adenosine Analogues on Glioma Cell Growth and Survival2.6 Conclusions and Future PerspectivesReferences3. CROSS-TALK IN NUCLEOTIDE SIGNALING IN GLIOMA C6 CELLSDorota Wypych and Jolanta Barańska Abstract3.1 Introduction3.2 Properties of P2 Receptors3.2.1 P2X Receptors3.2.2 P2Y Receptors3.3 P2Y1, P2Y2 and P2Y12 Rreceptor Expression and Functionality in Rat Glioma C6 cells3.4 Serum Withdrawal3.4.1 Effect on P2Y1 and P2Y12 Receptor Expression3.4.2 Effect on C6 cell Morphology, Growth and Differentiation3.4.3 Effect on the P2Y14 Receptor3.5 Cyclic AMP Effect on Cell Proliferation, Growth and Differentiation3.6 Effect of Extracellular Nucleotides on ERK1/2 and PI3K/Akt Activity: P2Y1 and P2Y12 Cross-Talk.3.7 The P2X7 Receptor3.8 Concluding RemarksReferences4. CALCIUM SIGNALING IN GLIOMA CELLS – THE ROLE OF NUCLEOTIDE RECEPTORSDorota Wypych and Pawel Pomorski Abstract4.1 Origin of the Calcium Signaling4.2 Sources of the Calcium Signal4.2.1 Extracellular Calcium Signal4.2.2 Signal Generated by Calcium Stores4.2.2.1 Store Operated Calcium Signaling4.2.2.2 Calcium-Induced Calcium Signaling4.3 Calcium Signaling in Non-Excitable Glial Cells4.3.1 Astrocytes4.3.2 Microglia4.4 Nucleotide Receptors-Evoked Calcium Signaling in Glial Cells4.5 Glioma C6: a Case Study4.5.1 The Nature of the Signal – the Role of Nucleotide Receptors in Glioma C6 Cells4.6 Gliomas: The Motile Tumors, Calcium Signaling and Chemotaxis4.6.1 The Calcium Signal in Glioma C6 is Strongly Dependent on Actin Cytoskeleton4.7 Concluding RemarksReferences5. PURINERGIC SIGNALING IN GLIOMA PROGRESSIONElizandra Braganhol, Márcia Rosângela Wink, Guido Lenz and Ana Maria Oliveira Battastini Abstract5.1 Introduction5.1.1 Molecular and Cellular Origins of Gliomas5.1.2 Glioma Cancer Stem Cells (CSCs)5.1.3 Tumor Microenvironment – Key for Understanding and Targeting Gliomas5.2 Purinergic Signaling in Gliomas5.3 Ectonucleotidases5.3.1 Ectonucleoside Triphosphate Diphosphohydrolases (E-NTPDases)5.3.2 Ectonucleotide Pyrophosphatase/Phosphodiesterases (E-NPPs)5.3.3 Ecto-Alkaline Phosphatases (ALP)5.3.4 Ecto-5’-Nucleotidase (ecto-5’-NT/CD73)5.4 Ecto-adenosine Deaminase (ecto-ADA)5.5 Other Ecto-Nucleotide Metabolizing Enzymes5.6 Ectonucleotidases in Gliomas5.7 The Purinergic Hypothesis of Glioma InvasionReferences6. CYTOSKELETON AND NUCLEOTIDE SIGNALING IN GLIOMA CELLSWanda Kłopocka, Jarosław Korczyński and Pawel Pomorski Abstract6.1 Introduction6.2 The Role of P2Y2 Receptor in Actin Cytoskeleton Organization6.2.1 Regulation by PIP2 6.2.2 Regulation by the Small GTP-binding Proteins: Rho, Rac and Cdc426.3 Compensation of ROCK Inhibition by P2Y2 Activated Signaling Pathways6.3.1 ROCK Inhibition in Glioma C6 Cells6.3.2 Effect of P2Y2 Receptor Stimulation on MLC Phosphorylation – the Role of MLCK6.3.3 Effect of P2Y2 Receptor Stimulation on Cofilin Phosphorylation – the Role of Rac1 Protein6.3.4 Effect of Calcium Signal on Glioma C6 Cells Recovery from ROCK Inhibition - Essential Role of Integrins6.4 SummaryReferences7. SIGNALING DETERMINANTS OF GLIOMA CELL INVASIONAneta Kwiatkowska and Marc Symons Abstract7.1 Invasiveness of Glioma Cells7.2 Factors that Control Glioma Invasion. 7.2.1 Autocrine Factors.7.2.2 Paracrine Factors.7.3 Signaling Mechanisms that Control Glioma Invasion.7.3.1 Integrins7.3.2 Rho GTPases7.3.3 PI3K and Phospholipid Signaling7.3.4 Akt Kinase7.4 Proteases7.5 Conclusions and Future DirectionsReferences8. RECEPTOR TYROSINE KINASES: PRINCIPLES AND FUNCTIONS IN GLIOMA INVASIONMitsutoshi Nakada, Daisuke Kita, Lei Teng, Ilya V. Pyko, Takuya Watanabe and Jun-ichiro HamadaAbstract8.1 Introduction8.2 EGFR/EGF8.3 PDGFR/PDGF 8.4 ERBB28.5 c-Met/HGF8.6 Tie/Ang8.7 Axl/Gas68.8 DDR1/Collagen8.9 Eph/Ephrin8.10 TrkA 8.11 Cross-Talk8.12 Targeting Receptor Type Tyrosine Kinases8.12.1 Targeting EGFR8.12.2 Targeting PDGFR8.12.3 Multiple Kinase Inhibitors8.13 ProspectiveReferences9. TGF BETA SIGNALING AND ITS ROLE IN GLIOMA PATHOGENESISBozena Kaminska and Magdalena Kijowska Abstract9.1 Introduction9.2 A Brief Summary of Mechanisms of TGF-b Signaling in Normal and Malignant Cells9.2.1 Components and Mechanisms of TGF-b Signaling9.2.2 Negative Regulators of TGF-b Signaling 9.2.3 Transcriptional Responses Induced by TGF-b Signaling. 9.3 Deregulation of TGF-b Signaling in Gliomas. 9.4 Functions of TGF-b Signaling in Glioma Biology9.4.1 TGF-b Signaling in Controlling Cell Proliferation9.4.2 TGF-b Signaling in the Regulation of Invasion9.4.3 TGF-β1 as Pro-Angiogenic Factor9.4.4 A Role of TGF-b Signaling in Glioma Cancer Initiating Cells9.4.5. TGF-b Signaling in Tumor-Mediated Immunosuppression9.5 Molecular and Pharmacological Strategies to Interfere with TGF-b Signaling for Potential Therapeutic Intervention in GliomasReferences10. STAT signaling in glioma cellsKarolina Swiatek-Machado and Bozena Kaminska Abstract10.1 Introduction 10.2 A Brief Summary of Mechanisms of STAT Activation in Normal and Malignant Signaling10.2.1 Mechanisms of STAT Activation10.2.2 Negative Regulators of STAT Signaling 10.2.3 Transcriptional Targets of STATs10.3 Dysfunction of STAT Signaling in Gliomas10.3.1 Constitutive Activation of STAT3 in Gliomas 10.3.2 STAT3 Activation in Gliomas Results from Dysfunction in Control Mechanisms10.4 Functions of STAT3 in Gliomas10.4.1 STAT3 as an Oncogene10.4.2 STAT3 as a Tumor Suppressor 10.4.3 STAT3 in Glioma Cancer Initiating Cells10.5 Molecular and Pharmacological Strategies to Interfere with STAT Signaling for Potential Therapeutic Intervention in GliomasReferences11. CANNABINOID SIGNALING IN GLIOMA CELLSAleksandra Ellert-Miklaszewska, Iwona Ciechomska and Bozena Kaminska Abstract11.1 Introduction11.2 Cannabinoids and their Receptors11.3 Cannabinoid System in Gliomas11.4 Action of Cannabinoids in Glioma Cells11.4.1 Mechanism of Cannabinoids Pro-Apoptotic Action – Inhibition of Pro-Survival Pathways11.4.2 The Role of ER Stress and Autophagy in Cannabinoid-Induced Cell Death11.5 Therapeutic Potential of Targeting Cannabinoid Signaling in GliomasReferences