Table Of ContentGlioma Signaling
Advances in Experimental Medicine and Biology
Editorial Board:
IRUN R. COHEN, The Weizmann Institute of Science, Rehovot, Israel
ABEL LAJTHA, N.S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA
JOHN D. LAMBRIS, University of Pennsylvania, Philadelphia, PA, USA
RODOLFO PAOLETTI, University of Milan, Milan, Italy
For further volumes:
http://www.springer.com/series/5584
Jolanta Barańska
Editor
Glioma Signaling
Editor
Jolanta Barańska
Biochemistry
Nencki Institute of Experimental
Biology
Warsaw, Poland
ISSN 0065-2598
ISBN 978-94-007-4718-0 ISBN 978-94-007-4719-7 (eBook)
DOI 10.1007/978-94-007-4719-7
Springer Dordrecht Heidelberg New York London
Library of Congress Control Number: 2012944755
© Springer Science+Business Media Dordrecht 2013
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Preface
The book Glioma Signaling re fl ects the need to bring together data covering the wide spectrum of
molecular mechanisms responsible for glioma physiology and pathobiology. It concentrates on
regulation of glioma growth, progression and invasion, areas where studies have reached the stage of
critical evaluation.
The book is divided in two parts. The fi rst half (Chaps. 1 , 2 , 3 , 4 , 5 and 6 ) is focused on the
mechanism of nucleotide receptor signaling. It is introduced by Chap. 1 , in which Geoffrey Burnstock
presents nucleotide signaling in the brain. Burnstock was the fi rst who, in the 1970s, discovered the
role of ATP as a transmitter in the nervous system and termed a large family of the responding recep-
tors “purinergic”. Since it was later shown that not only adenine but also uridine extracellular nucle-
otides act on the same class of receptors, they are presently termed “nucleotide receptors” although
the previous designation is still used. Chapter 1 introduces the reader to the nucleotide signaling in the
brain, both in neurons and glial cells, its involvement in co-transmission, neuron-glia interaction and
pathobiology, including gliomas.
Chapters 2 and 3 are focused on P1 and P2 nucleotide receptor signaling in glioma cells, respectively.
In Chap. 2 , adenosine signaling by A , A , A and A subtypes of P1 receptor and pathways control-
1 2A 2B 3
ling survival and death of astrocytoma cells are presented. The A receptor, highly expressed in a
3
variety of cancer cell lines and characterized by strong pro-apoptotic effects, is suggested as a possible
new target for chemotherapy of brain tumors. Chapter 3 dwells on the expression and functionality of
P2 receptors activated by extracellular ATP, ADP, UTP and UDP, and describes the molecular mecha-
nisms of P2Y and P2Y cross-talk, proposed to be involved in cell survival, proliferation and
1 12
up-regulated growth, in glioma C6 cells.
The next three chapters concentrate on special aspects of nucleotide receptor activity in glioma
cells, such as generation of calcium signals (Chap. 4 ), cross-talk with ecto-enzyme activity (Chap. 5 )
and modulation of actin cytoskeleton dynamics (Chap. 6 ). Moreover, Chap. 4 compares the nature of
calcium signals in glioma cells with that in astrocytes and microglia, whereas Chap. 6 presents the
peculiar role of the P2Y receptor in the cross-talk between pathways that regulate C6 cell cytoskel-
2
eton. Chapter 5 shows the effect of ATP and AMP degradation by ecto-nucleotidases on tumor growth.
In comparison to astrocytes, gliomas have low ATPase and high AMPase activity. Such alterations in
extracellular ATP metabolism, associated with P1 and P2 nucleotide receptor activity, are suggested
to play an important role in glioma progression.
In the second half of the book (Chaps. 7 , 8 , 9 , 1 0 and 11 ) authors’ attention is concentrated on sig-
naling induced by growth factors, cytokines and cannabinoids and their role in glioma pathobiology.
Chapters 7 and 8 provide new data concerning signaling determinants and functions of receptor tyrosine
kinases in glioma cell invasion, describe signaling elements stimulated by integrins (Chap. 7 ), and
v
vi Preface
discuss in details the role of different growth factor receptors and multiple kinase inhibitors in glioma
invasion (Chap. 8 ). Both chapters present recent advances in the understanding of the molecular mech-
anism controlling glioma invasion and suggest personalized anti-invasion therapies for genetically
distinct subgroups of patients.
Chapter 9 deals with transforming growth factor beta (TGFb ), a multifunctional cytokine, activat-
ing membrane serine/threonine kinase receptors and leading to the activation of the cytoplasmic
transcription factor, SMAD. TGFb plays a special role in oncogenesis – being a strong proliferation
inhibitor for endothelial cells and astrocytes, it acts as a tumor suppressor on many tumor cells,
especially high-grade gliomas. STAT (signal transducer and activator of transcription) protein family
is another group of cytoplasmic transcription factors, which function as downstream effectors of
cytokine and growth factor receptor signaling. The mechanisms, complexity and dysfunction of STAT
signaling in gliomas and its role in pathobiology are described in Chap. 1 0 .
The book ends with a description of cannabinoid signaling at the molecular level. Cannabinoids are
currently considered as anti-cancer agents. Chapter 1 1 describes anti-survival, pro-apoptotic and anti-
proliferative effects of cannabinoids on glioma cells and suggests their high therapeutic potential.
Thus, Glioma Signaling summarizes a number of subjects of interest to both scienti fi c and clinical
investigators. Since glioma is a group of brain tumors very refractory to conventional treatments, such
as surgery, radiotherapy and chemotherapy, the search for new directions in glioma therapy is still
needed. Data presented in this book give some hope that investigations in the area of molecular biol-
ogy and neurobiology, concerning mechanisms of intracellular signaling responsible for glioma
pathogenesis, up-regulated growth, progression and invasion, will bene fi t glioma patients.
With grateful thanks to all authors for their cooperation and to Springer SBM for encouraging me
to undertake the effort of preparing this book.
Jolanta Barańska
Editor
Contents
1 Introduction to Purinergic Signalling in the Brain .......................................................... 1
Geoffrey Burnstock
2 Adenosine Signaling in Glioma Cells ................................................................................ 13
Stefania Ceruti and Maria P. Abbracchio
3 Cross-Talk in Nucleotide Signaling in Glioma C6 Cells .................................................. 31
Dorota Wypych and Jolanta Barańska
4 Calcium Signaling in Glioma Cells – The Role of Nucleotide Receptors....................... 61
Dorota Wypych and Paweł Pomorski
5 Purinergic Signaling in Glioma Progression .................................................................... 81
Elizandra Braganhol, Márcia Rosângela Wink, Guido Lenz,
and Ana Maria Oliveira Battastini
6 Cytoskeleton and Nucleotide Signaling in Glioma C6 Cells ........................................... 103
Wanda Kłopocka, Jarosław Korczyński, and Paweł Pomorski
7 Signaling Determinants of Glioma Cell Invasion ............................................................. 121
Aneta Kwiatkowska and Marc Symons
8 Receptor Tyrosine Kinases: Principles and Functions in Glioma Invasion .................. 143
Mitsutoshi Nakada, Daisuke Kita, Lei Teng, Ilya V. Pyko, Takuya Watanabe,
Yutaka Hayashi, and Jun-ichiro Hamada
9 TGF Beta Signaling and Its Role in Glioma Pathogenesis .............................................. 171
Bozena Kaminska, Marta Kocyk, and Magdalena Kijewska
10 STAT Signaling in Glioma Cells ........................................................................................ 189
Karolina Swiatek-Machado and Bozena Kaminska
11 Cannabinoid Signaling in Glioma Cells ............................................................................ 209
Aleksandra Ellert-Miklaszewska, Iwona Ciechomska, and Bozena Kaminska
Index ............................................................................................................................................. 221
vii
Contributors
Maria P. Abbracchio Laboratory of Molecular and Cellular Pharmacology of Purinergic
Transmission, Department of Pharmacological and Biomolecular Sciences , Università degli Studi di
Milano , Milan , Italy
Jolanta Barańska Nencki Institute of Experimental Biology , Polish Academy of Sciences , Warsaw ,
Poland
Ana Maria Oliveira Battastini Departamento de Bioquímica , ICBS, Universidade Federal do Rio
Grande do Sul , Porto Alegre , RS, Brazil
Elizandra Braganhol Centro de Ciências Químicas, Farmacêuticas e de Alimentos (CCQFA) ,
Universidade Federal de Pelotas (UFPel) , Capão do Leão , RS , Brazil
Geoffrey Burnstock Autonomic Neuroscience Centre , University College Medical School ,
London , UK
Stefania Ceruti Laboratory of Molecular and Cellular Pharmacology of Purinergic Transmission,
Department of Pharmacological and Biomolecular Sciences , Università degli Studi di Milano , Milan ,
Italy
Iwona Ciechomska Laboratory of Transcription Regulation, Department of Cell Biology , Nencki
Institute of Experimental Biology, Polish Academy of Sciences , Warsaw , Poland
Aleksandra Ellert-Miklaszewska Laboratory of Transcription Regulation, Department of Cell
Biology , Nencki Institute of Experimental Biology, Polish Academy of Sciences , Warsaw , Poland
Jun-ichiro Hamada Department of Neurosurgery, Division of Neuroscience, Graduate School
of Medical Science , Kanazawa University , Kanazawa , Ishikawa , Japan
Yutaka Hayashi Department of Neurosurgery, Division of Neuroscience, Graduate School
of Medical Science , Kanazawa University , Kanazawa , Ishikawa , Japan
Bozena Kaminska Laboratory of Transcription Regulation, Department of Cell Biology , Nencki
Institute of Experimental Biology, Polish Academy of Sciences , Warsaw , Poland
Magdalena Kijewska Laboratory of Transcription Regulation, Department of Cell Biology, , Nencki
Institute of Experimental Biology, Polish Academy of Sciences , Warsaw , Poland
Daisuke Kita Department of Neurosurgery, Division of Neuroscience, Graduate School of Medical
Science , Kanazawa University , Kanazawa , Ishikawa , Japan
ix
x Contributors
Wanda Kłopocka Nencki Institute of Experimental Biology , Polish Academy of Sciences , Warsaw ,
Poland
Marta Kocyk Laboratory of Transcription Regulation, Department of Cell Biology, Nencki Institute
of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland
Jarosław Korczyński Nencki Institute of Experimental Biology , Polish Academy of Sciences ,
Warsaw , Poland
Aneta Kwiatkowska Center for Oncology and Cell Biology, Laboratory for Brain Tumor Biology,
Feinstein Institute for Medical Research , Manhasset , NY , USA
Guido Lenz Departamento de Biofísica, IB e Centro de Biotecnologia , Universidade Federal do Rio
Grande do Sul , Porto Alegre , RS , Brazil
Mitsutoshi Nakada Department of Neurosurgery, Division of Neuroscience, Graduate School
of Medical Science , Kanazawa University , Kanazawa , Ishikawa , Japan
Paweł Pomorski Laboratory of Transcription Regulation, Department of Cell Biology, Nencki
Institute of Experimental Biology , Polish Academy of Sciences , Warsaw , Poland
Ilya V. Pyko Department of Neurosurgery, Division of Neuroscience, Graduate School of Medical
Science , Kanazawa University , Kanazawa , Ishikawa , Japan
Karolina Swiatek-Machado Nencki Institute of Experimental Biology , Polish Academy of Sciences ,
Warsaw , Poland
Marc Symons Center for Oncology and Cell Biology, Laboratory for Brain Tumor Biology, Feinstein
Institute for Medical Research , Manhasset , NY , USA
Lei Teng Department of Neurosurgery, Division of Neuroscience, Graduate School of Medical
Science , Kanazawa University , Kanazawa , Ishikawa , Japan
Department of Neurosurgery, The First Clinical College of Harbin Medical University, Harbin,
Heilongjiang Province, People’s Republic of China
Takuya Watanabe Department of Neurosurgery, Division of Neuroscience, Graduate School
of Medical Science , Kanazawa University , Kanazawa , Ishikawa , Japan
Márcia Rosângela Wink Departamento de Ciências Básicas da Saúde , Universidade Federal de
Ciências da Saúde de Porto Alegre , Porto Alegre , RS , Brazil
Dorota Wypych Nencki Institute of Experimental Biology , Polish Academy of Sciences , Warsaw ,
Poland
Laboratory of Molecular and Cellular Pharmacology of Purinergic Transmission, Department of
Pharmacological and Biomolecular Sciences , U niversità degli Studi di Milano , Milan , Italy
