Angiogenesis, Lymphangiogenesis and Clinical Implications

Sommaire et contenu du livre "Angiogenesis, Lymphangiogenesis and Clinical Implications"

Angiogenesis, Lymphangiogenesis and Clinical Implications
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Chemical Immunology and Allergy

Vol. 99
Series Editors


Johannes Ring Munich Kurt Blaser Davos Monique Capron Lille Judah A. Denburg Hamilton Stephen T. Holgate Southampton Gianni Marone Naples Hirohisa Saito Tokyo

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Angiogenesis, Lymphangiogenesis and Clinical Implications
Volume Editors
Gianni Marone Naples Francescopaolo Granata Naples
26 figures, 14 in color and 8 tables, 2014

Basel · Freiburg · Paris · London · New York · New Delhi · Bangkok · Beijing · Tokyo · Kuala Lumpur · Singapore · Sydney

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Chemical Immunology and Allergy
Formerly published as ‘Progress in Allergy’ (Founded 1939),
continued 1990–2002 as ‘Chemical Immunology’
Edited by Paul Kallós 1939–1988, Byron H. Waksman 1962–2002

Gianni Marone Francescopaolo Granata
Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research University of Naples Federico II School of Medicine Naples (Italy)
Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents ® and PubMed/MEDLINE.
Disclaimer. The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
© Copyright 2014 by S. Karger AG, P.O. Box, CH–4009 Basel (Switzerland) www.karger.com Printed in Germany on acid-free and non-aging paper (ISO 9706) by Kraft Druck GmbH, Ettlingen ISSN 1660–2242 e-ISSN 1662–2898 ISBN 978–3–318–02480–7 e-ISBN 978–3–318–02481–4

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To Graziella Persico whose life and science continue to inspire us


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Contents

XI Preface
Marone, G.; Granata, F. (Naples)
1 History of Research on Angiogenesis
Ribatti, D. (Bari)
1 Abstract
2 First Isolation of an Endothelial Cell
2 Development of in vivo Assays for the Study of Angiogenesis
4 Isolation of Basic Fibroblast Growth Factor
4 Isolation of Vascular Permeability Factor/Vascular Endothelial Growth Factor
5 Isolation of Placental Growth Factor
5 Early Evidence of Tumor Cells Releasing Specific Growth Factor for Blood Vessels
6 Absence of Angiogenesis in Tumors in Isolated Perfused Organs and First Evidence of the Existence
of the Avascular and Vascular Phases in Solid Tumor Growth
7 First Formulation of the Hypothesis that Tumor Growth Is Angiogenesis Dependent and Isolation
of the First Tumor Angiogenic Factor
7 Prognostic Significance of Tumor Vascularity
8 Antiangiogenesis
13 References
15 Immune Cells as a Source and Target of Angiogenic and Lymphangiogenic
Factors
Loffredo, S.; Staiano, R.I.; Granata, F.; Genovese, A.; Marone, G. (Naples)
15 Abstract
17 Expression of VEGFs and Their VEGFRs in Mast Cells
19 Expression of VEGFs, Their VEGFRs and NRPs in Human Basophils
20 Expression of VEGFs and VEGFRs in Monocytes, Macrophages and Dendritic Cells
20 Monocytes
20 Macrophages
21 Angiogenic Activity of Macrophages
23 Antiangiogenic Activity of Macrophages
23 Lymphangiogenic Activity of Macrophages
24 Dendritic Cells
24 Expression of NRPs in Regulatory T Cells
25 Expression of Angiopoietins in Immune Cells
25 Mast Cells and Basophils
26 Eosinophils
26 Neutrophils
26 Macrophages
27 Direct and Indirect Angiogenic Activity of IL-17


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28 IL-17E/IL-25 Promotes Angiogenesis in Asthma
28 IL-17E/IL-25 Production by Human Eosinophils and Basophils
28 Concluding Remarks
30 Acknowledgements
30 References
37 Neuropilins: Role in Signalling, Angiogenesis and Disease
Zachary, I. (London)
37 Abstract
38 Neuropilin Structure
40 Neuropilin Ligands
40 Semaphorins
40 VEGFs
42 NRP Genomic Organisation and Isoforms
45 Neuropilin Function in Development
48 Receptors and Signalling Mechanisms
48 Plexins
49 L1 CAM
50 VEGF Signalling
52 Role of the NRP Cytosolic Domain
54 NRP Regulation of Cell Migration
55 Other Cell Functions
56 Neuropilin Functions in Disease and Adult Tissues
56 Cancer
58 Immune System
59 Wound Healing
60 Liver Cirrhosis
60 Other Functions
60 Conclusions and Perspectives
61 Acknowledgements
62 References
71 Class 3 Semaphorin in Angiogenesis and Lymphangiogenesis
Bussolino, F. (Candiolo); Giraudo, E. (Candiolo/Torino); Serini, G. (Candiolo)
71 Abstract
72 Semaphorins and Their Receptors
75 Class 3 Semaphorin
76 Semaphorins Control Vascular Development
77 Semaphorins and Lymphatic Development
78 Semaphorins and Tumor Angiogenesis
81 Semapahorins in Revascularization of Ischemic Tissues
82 Conclusion
83 Note Added in Proof
83 Acknowledgements
83 References
89 Angiogenic and Antiangiogenic Chemokines
Bosisio, D.; Salvi, V.; Gagliostro, V. (Brescia); Sozzani, S. (Brescia/Rozzano)
89 Abstract
89 Chemokine System
92 Cell Activation by Chemokine Receptors
93 Chemokines in Angiogenesis
96 Chemokines in Tumor Angiogenesis
96 Tumor-Associated Leukocytes and Angiogenesis
98 Direct Induction of Angiogenesis by Tumor Cells

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99 Chemokines in Lymphangiogenesis
99 Nonchemokine Chemoattractants in Angiogenesis
101 Concluding Remarks
102 References
105 Role of uPA/uPAR in the Modulation of Angiogenesis
Montuori, N. (Naples); Ragno, P. (Salerno)
105 Abstract 106 Plasminogen Activation System 108 uPA Receptor 110 uPA/uPAR Functions 112 uPA/uPAR in Angiogenesis 116 uPA-uPAR in Endothelial Progenitor Cells 117 PAI1 and Angiogenesis 118 Conclusions 119 References
123 Neutrophil-Derived Cytokines Involved in Physiological and Pathological Angiogenesis
Tecchio, C.; Cassatella, M.A. (Verona)
123 Abstract 124 VEGF: A Key Molecule for Neutrophil-Mediated Angiogenesis 125 Physiological Conditions 126 Pathological Conditions 128 PK2/BV8: A Recently Uncovered Mediator of Neutrophil-Induced Angiogenesis 128 Physiological Conditions 129 Pathological Conditions 129 Other Neutrophil-Derived Cytokines and Chemokines with Proangiogenetic Activity 129 CXCL8/IL-8 130 Oncostatin M 131 Neutrophil-Derived Proangiogenic Cytokines Awaiting Further Research in the Angiogenesis Field 131 Fibroblast Growth Factor-2 132 Angiopoietin 1 132 Interleukin-17 132 Conclusions 133 Acknowledgements 134 References
138 Roles of Eosinophils in the Modulation of Angiogenesis
Nissim Ben Efraim, A.H.; Levi-Schaffer, F. (Jerusalem)
138 Abstract 138 Allergic Inflammation 140 Angiogenesis and Allergic Inflammation 141 Eosinophils 143 Eosinophils and Angiogenesis 146 Hypoxia and Eosinophils 149 Acknowledgement 149 References
155 Regulatory T Cells, Leptin and Angiogenesis
Pucino, V.; De Rosa, V.; Procaccini, C. (Napoli); Matarese, G. (Salerno)
155 Abstract 155 Regulatory T Cells, Leptin and Metabolic Regulation 158 Leptin, Endothelial Cell Function and Angiogenesis

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159 Angiogenic Factors Expressed by Treg Cells: Neuropilin-1, VEGF and Leptin 162 Antiangiogenic Drugs and Their Involvement in Treg Cell-Mediated Immune Modulation 163 Treg Cells and Tumor Progression 164 Conclusions and Perspectives 165 Acknowledgements 165 References
170 Angiogenesis as a Therapeutic Target for Obesity and Metabolic Diseases
Cao, Y. (Stockholm/Linköping)

170 Abstract 172 Adipose Vasculature 173 Angiogenic Factors, Cytokines and Adipokines 175 Paradoxical Principles in Treatment of Obesity and Metabolic Disease 177 Angiogenesis as a Therapeutic Target for Obesity-Associated Disorders 177 Perspectives 178 Acknowledgements 178 References
180 Angiogenesis in Multiple Myeloma
Vacca, A.; Ria, R.; Reale, A.; Ribatti, D. (Bari)

180 Abstract 180 First Evidence of an Increased Angiogenesis in Bone Marrow of Multiple Myeloma Patients 181 Factors Involved in the Angiogenic Switch 184 Genomic Studies in MM 185 Role of Bone Marrow Endothelial Cells 186 Role of Circulating Endothelial Cells and Endothelial Precursor Cells 187 Role of Bone Marrow Microenvironment 188 Hypoxia 188 Clinical Evidence 190 Antiangiogenesis in Multiple Myeloma 192 Concluding Remarks 192 Acknowledgements 192 References
197 Angiogenesis Inhibitors in the Treatment of Prostate Cancer
Adesunloye, B.A.; Karzai, F.H.; Dahut, W.L. (Bethesda, Md.)

197 Abstract 198 Angiogenesis 198 Role of Angiogenesis in Prostate Cancer 200 VEGF Targeting Agents 200 Bevacizumab 201 VEGF-Trap 201 PI-88 202 Tyrosine Kinase Inhibitors 202 Sorafenib 202 Sunitinib 203 Cediranib 203 Cabozantinib 204 Semaxinib 204 Immunomodulatory Agents 204 Thalidomide 205 Lenalidomide 205 Tasquinimod 206 Tumor Vascular Disrupting Agent 206 Vadimezan
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207 Miscellaneous Agents 207 J591 207 TRC105 208 Itraconazole 208 Sodium Selenate 209 Cilengitide 209 TNP-470 209 Conclusion 211 References
216 Therapeutic Perspectives in Vascular Remodeling in Asthma and Chronic Obstructive Pulmonary Disease
Olivieri, D.; Chetta, A. (Parma)
216 Abstract 216 Vascular Remodeling in Asthma 219 Vascular Remodeling in Chronic Obstructive Pulmonary Disease 220 Effects on Vascular Remodeling of the Currently Used Drugs in Asthma and Chronic Obstructive
Pulmonary Disease 222 Potential Therapeutic Implications of Bronchial Vascular Remodeling 223 Conclusions 223 References
226 Author Index
227 Subject Index

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Preface

Angiogenesis, namely the formation of blood vessels, plays a fundamental role in such diverse physiological processes as embryonic and postnatal development, reproduc­tive functions, and wound repair. It was Judah Folkman who, in 1971, first suggested that angiogenesis is a major factor also in tumor growth, and proposed that blockade of angiogenesis might represent a novel therapy for solid tumors. Since then, we have witnessed explosive progress in our understanding of the molecular mechanisms governing the growth and differentiation of new blood vessels.
A major breakthrough in this field came when Harold Dvorak and collaborators purified and named the vascular permeability factor that was later cloned and desig­nated ‘vascular endothelial growth factor’ (VEGF), which is the most potent proan­giogenic mediator known so far. The VEGF family is constituted by five members (VEGF-A, VEGF-B, VEGF-C and VEGF-D) and placental growth factor. Placental growth factor was identified and named by the late Graziella Persico, an extraordi­nary and brilliant investigator to whom this volume is dedicated. Evidence obtained in recent years indicates that the lymphatic vascular system is crucial not only in tu­mor growth and the formation of metastases, but also for the modulation of immune functions and fat metabolism. Although VEGF-C and VEGF-D are the key growth factors that can directly stimulate lymphatic endothelial cells, the other growth fac­tors have also been implicated in lymphangiogenesis.
Notwithstanding the concept that both angiogenesis and lymphangiogenesis are essential for tumor growth, there is increasing evidence that the two aspects play an important role in an increasing number of immune disorders and metabolic diseases. Another important issue is the observation that although tumors are a major source of angiogenic/lymphangiogenic factors, several cells of the innate and adaptive im­mune system can produce a distinct set of these factors. Moreover, it has been shown that several angiogenic/lymphangiogenic factors can exert a variety of proinflamma­tory effects by engaging VEGF receptors and angiopoietin receptors (Tie1 and Tie2) present on immune cells.
Given the rapid advances made in this field, it is difficult to produce a timely refer­ence text and a comprehensive overview of the field. Despite these difficulties, I ac­cepted the invitation of the editors of the Chemical Immunology series to produce a
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volume entitled ‘Angiogenesis, Lymphangiogenesis and Clinical Implications’. This work was designed to highlight some of the results obtained mainly with human im­mune cells as a source and target of angiogenic and lymphangiogenic factors. The clinical part of the volume deals with some of the disorders in which treatment with antiangiogenic molecules appears to be promising.
It is already obvious that several issues remain to be solved in this area. The spec­trum of angiogenic and lymphangiogenic factors produced by the different compo­nents of the human innate and adaptive immune system is still largely unknown. Similarly, the specific and selective distribution of receptors and coreceptors for the different angiogenic and lymphangiogenic molecules on immune cells is incomplete. Moreover, it is becoming evident that there are striking differences in the mediators and their receptors between human and rodent immune cells. Although angiogenesis and lymphangiogenesis are important in tissue remodeling in certain chronic in­flammatory disorders (e.g. bronchial asthma, rheumatoid arthritis, psoriasis), it is still unknown whether alterations of angiogenesis and lymphangiogenesis could be a target in these disorders.
Many contributors to this volume are working or have worked in Italian research centers. This probably reflects the fact that thanks to Graziella Persico, many of her friends and pupils found the various aspects of angiogenesis and lymphangiogenesis a fertile field of study.
I would like to thank Karger Publishers and their staff for their assistance through­out the production of this volume. This volume owes much to the stimulating intel­lectual environment provided by our collaborators at the Division of Clinical Immu­nology and the Center for Basic and Clinical and Immunology Research (CISI) of the University of Naples ‘Federico II’.
Gianni Marone, NaplesFrancescopaolo Granata, Naples

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