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Angiogenesis Molecular Biology, Clinical Aspects NATO ASI Series Advanced Science Institutes Series A series presenting the results of activities sponsored by the NA TO Science Committee, which aims at the dissemination of advanced scientific and technological knowledge, with a view to strengthening links between scientific communities. The series is published by an international board of publishers in conjunction with the NATO Scientific Affairs Division A Life Sciences Plenum Publishing Corporation B Physics New York and London C Mathematical and Physical Sciences Kluwer Academic Publishers D Behavioral and Social Sciences Dordrecht, Boston, and London E Applied Sciences F Computer and Systems Sciences Springer-Verlag G Ecologiqal Sciences Berlin, Heidelberg, New York, London, H Cell Biology Paris, Tokyo, Hong Kong, and Barcelona I Global Environmental Change Recent Volumes in this Series Volume 257 - Vascular Endothelium: Physiological Basis of Clinical Problems II edited by John D. Catravas, Allan D. Callow, and Una S. Ryan Volume 258 - A Multidisciplinary Approach to Myelin Diseases II edited by S. Salvati Volume 259 - Experimental and Theoretical Advances in Biological Pattern Formation edited by Hans G. Othmer, Philip K. Maini, and James D. Murray Volume 260 - Lyme Borreliosis edited by John S. Axford and David H. E. Rees Volume 261 - New Generation Vaccines: The Role of Basic Immunology edited by Gregory Gregoriadis, Brenda McCormack, Anthony C. Allison, and George Poste Volume 262 - Radiolabeled Blood Elements: Recent Advances in Techniques and Applications edited by J. Martin-Comin, M. L. Thakur, C. Piera, M. Roca, and F. Lomeiia Volume 263 - Angiogenesis: Molecular Biology, Clinical Aspects edited by Michael E. Maragoudakis, Pietro M. Gullino, and Peter I. Lelkes Series A: Life Sciences Angiogenesis Molecular Biology, Clinical Aspects Edited by Michael E. Maragoudakis University of Patras Medical School Patras, Greece Pietro M. Gullino University of Torino Medical School Torino, Italy and Peter I. Lelkes University of Wisconsin Medical School Milwaukee, Wisconsin Springer Science+Business Media, LLC Proceedings of a NATO Advanced Study Institute on Angiogenesis: Molecular Siology, Clinical Aspects, held June 16-27, 1993, in Rhodes, Greece NATO-PCO-DATA BASE The electronic index to the NATO ASI Series provides full bibliographical references (with keywords and/or abstracts) to more than 30,000 contributions from international scientists published in aII sections of the NATO ASI Series. Access to the NATO·PCO·DATA SASE is possible in two ways: -via online FILE 128 (NATO-PCO-DATA SASE) hosted by ESRIN, Via Galileo Galilei, 1-00044 Frascati, Italy -via CD·ROM "NATO Science and Technology Disk" with user-friendly retrieval software in English, French, and German (©WTV GmbH and DATAWARE Technologies, Inc. 1989). The CD-ROM also contains the AGARD Aerospace Database. The CD-ROM can be ordered through any member of the Board of Publishers or through NATO-PCO, Overijse, Belgium. Additional material to this book can be downloaded from http://extras.springer.com Llbrary of Congress Cataloglng-ln-Publlcatlon Data Anglogenesls : molecular blology, cllnlcal aspects I edlted by Mlchael E. Maragoudakls, Pletro M. Gulllno, and Peter 1. Lelkes. p. cm. -- (NATD ASI serles. Serles A: Llfe sclences, voI. 263. ) 'Proceedlngs of a NATD Advanced Study Institute on anglogenesls: ~olecular blology, cllnlcal aspects, held June 16-27, 1993, In Rhodes, Greece" -- T.p. verso. Includes bibllographlcal references and Index. ISBN 978-1-4757-9190-7 ISBN 978-1-4757-9188-4 (eBook) DOI 10.1007/978-1-4757-9188-4 1. Neovascularlzatlon--Congresses. 1. Maragoudakls, Mlchael E. II. Gulllno, Pletro M. III. Lelkes, Peter 1. IV. Serles: NATD advanced sclences lnstltutes ser Ies. Serles A, Llfe sclences ; v. 263. QP106.6.A55 1994 612.1'3--dc20 94-10036 CIP ISBN 978-1-4757-9190-7 ©1994 Springer Science+Business Media New York Originally published by Plenum Press, New York in 1994 Softcover reprint of the hardcover 1s t edition 1994 AII rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher PREFACE Angiogenesis is a multistep process, which involves activation, proliferation and directed migration of endothelial cells to form new capillaries from existing vessels. Under physiological conditions, in the adult organisms angiogenesis is extremely slow, yet it can be activated for a limited time only in situations such as ovulation or wound healing. In a number of disease states, however, there is a derangement of angiogenesis, which can contribute to the pathology of these conditions. Hence, understanding the molecular biology of endothelial cell activation and differentiation and the mechanisms involved in the regulation of angiogenesis, could explain the derangement in disease states and also provide the basis for developing promoters or suppressors of angiogenesis for clinical applications. This book contains the proceedings of the NATO Advanced Study Institute on "Angiogenesis: Molecular Biology, Oinical Aspects" held in Rhodes, Greece, from June 16-27, 1993. This meeting was a comprehensive review of the various aspects of angiogenesis such as embryonic development, endothelial cell heterogeneity and tissue specificity, molecular biology of endothelial cell, mechanisms for the regulation of angiogenesis, disease states in which angiogenesis is involved and potential application of promoters or suppressors of angiogenesis. The presentations and discussions of the meeting provided an opportunity for investigators from many different areas of basic science and medicine to exchange information, evaluate the present status and provide future research directions in the field of angiogenesis. I wish to thank Drs. Pietro Gullino and Peter Lelkes, co-Directors of this meeting and the International Organizing Committee that included Drs. Robert Auerbach, Francoise Dieterlen, Juliana Denekamp and Peter Polverini for their help in organizing the meeting. I thank also all the participants for their enthusiastic participation and their complimentary comments on the success of this conference. In addition, I thank the Scientific Affairs Division of NATO who provided the funds for publication of this book and the major portion of the funds for the organization of the meeting. The contribution of the following organizations: Boehringer (Greece), British Council (Greece), Bristol-Meyers-Squibb (Greece), Ciba-Geigy (Greece), Council of Tabaco Res. (USA), Farmitalia (Italy), Galenica (Greece), Genentech (U.S.A.), Genetech (USA), Gibco Life Technology (USA), Help (Greece), Hoechst (Greece), Jensen (Greece), Lilly Ltd (UK), Pfizer (USA), Promega (USA), Spinx Pharm. Corp. (USA), Sandoz (Greece), Smith Kline and French Beecham (Greece), Upjohn (U.S.A.), and Zeneca Pharmac. (UK), which was used to support the participation of many young scientists, is gratefully acknowledged. For travel arrangements and the daily operations of the conference I am thankful to Mrs. Lydia Argyropoulou. I am particularly grateful to Mrs. Anna Marmara for her dedicated and enthusiastic work throughout the organization of the meeting and the editing of this monograph. Michael E. Maragoudakis (Greece) v CONTENTS EMBR YONIC DEVELOPMENT AND ANGIOGENESIS Embryology of the Endothelial Network: Is There an Hemangioblastic Anlage? ........................................................................ 1 F. Dieterlen-Lievre, D. Luton, and L. Pardanaud Cellular and Molecular Biology of Endothelial Cell Differentiation during Embyronic Development ........................ ........ 9 TJ. Poole Endothelial Cell Heterogeneity and Organ Specificity................................. ...... 15 P. I. Lelkes, V.G. Manolopoulos, D. Chick, and B. R. Unsworth MOLECULAR BIOLOGY OF ANGIOGENESIS Inhibitors of Neovascularization: Critical Mediators in the Coordinate Regulation of Angiogenesis ............................................... 29 P. Polverini Human Basic Fibroblast Growth Factor: Structure-Function Relationship of an Angiogenic Molecule ...................................... ........ 39 M. Presta, M. Rusnati, A. Gualandris, P. Dell'Era, e. Urbinati, D. Coltrini, E. Tanghetti, and M. Belleri Angiogenesis Models Identify Factors which Regulate Endothelial Cell Differentiation......................... .... ............................... 51 D.S. Grant, D. Morales, M.e. Cid and H.K. Kleinman EMA-l, a Novel Endothelial Cell Surface Molecule That Is Preferentially Expressed by Migrating Endothelial Cells........................................................................................................... 61 H.G. Augustin-Voss, and B.U. Pauli Early Response Genes in Endothelial Cells ........................................................ 67 T. Hla PIGF: Placenta Derived Growth Factor ............................................................ 73 D. Maglione and M.G. Persico vii Expression of the M-Subunit of Laminin Correlates with Increased Cell Adhesion and Metastatic Propensity ................................................................................................ 81 W. Jenq, S.J. Wu, and N. A. Kefalides The Proliferative Effect of Substance P on Capillary Endothelial Cells Is Mediated by Nitric Oxide ....... ... ......... .... .... ..... ...... 91 M. Ziche, L. Morbidelli, L. Mantelli, E. Masini, F. Ledda, H.J. Granger, and C.A. Maggi Reactivation of Metalloproteinase-Inhibitor Complex by a Low Molecular Mass Angiogenic Factor ............................................... 97 B. McLaughlin and J.B. Weiss Interactions between Oxidized Lipoprotein(a) [Lp(a)] Monocytes and Endothelial Cells............................................................ 103 M. Ragab, P. Selvaraj and D. Sgoutas Altered Proliferation of Retinal Microvascular Cells in Response to Non-Enzymatic Glycosylated Matrix Proteins ....... ........... .... ....... ...... ....... ........... ............. .... .... ... ......... ...... ....... 111 T.A. Kalfa, M.E. Genitsen and E.e. Tsilibari A Novel Laminin Domain Involved in Adhesion of Endothelial Cells .................................................................................... 119 A. Charonis, N. Koliakos, G. Koliakos, G. Fields, L. Regger, e. Lynch, M. Spreeman, A. Hunter and H. Higson REGULATION OF ANGIOGENESIS Regulation of Angiogenesis: The Role of Protein Kinase, Nitric Oxide, Thrombin and Basement Membrane Synthesis ............. 125 M.E. Maragoudakis, N. Tsopanoglou, G. HaralabopoulQs, E. Sakkoula, E. Pipili-Synetos, and E. Missirlis Basement Membrane Laminin-Derived Peptide SIKV A V Promotes Angiogenesis and Tumor Growth......................................... 135 H.K. Kleinman, D.S. Grant, and M.e. Kibbey Release of Gangliosides in the Microenvironment and Angiogenic Response in Vivo- ............................................................... 143 P.M. Gullino Angiogenesis in Vitro: Cytokine Interactions and Balanced Extracellular Proteolysis ...................................................................... 149 M.S. Pepper, J.D. Vassalli, L. Orci, and R. Montesano Endothelial Plasminogen Activators and Matrix Metalloproteinases in Fibrinolysis and Local Proteolysis ................................................................................................ 171 V.W.M. van Hinsbergh, R. Hanemaaijer, and P. Koolwijk viii ANGIOGENESIS AND DISEASE STATES Tumor Antiangiogenesis: Which Way?............................................................... 183 P. M. Gullino Therapeutic Angiogenesis in Surgery and Oncology......................................... 193 M. Hockel, K. Schlenger, R. Frischmann-Berger, S. Berger and P. Vaupel Endothelial Cell Stimulating Angiogenesis Factors in Relation to Disease Processes .... ....... ... ............ ... ... .... ..... .... ..... ....... ..... 209 J. B. Weiss Hyaluronan and Angiogenesis: Molecular Mechanisms and Clinical Applications................................................................................. 219 S. Kumar, 1. Ponting, P. Rooney, P. Kumar, D. Pye, and M. Wang Chronic Cellular Injury and Human Proliferative Disorders... ..... ...... ... ..... .... .... ....... ... ...................... .............. ..... ..... ........ .... 233 H. Antoniades Cellular and Molecular Mechanisms of Angiogenesis in the Brain .......................................................................................................... 239 A. M. Tsanac1is Angiogenesis and Fibrin Degradation in Human Breast Cancer....................................................................................................... 245 W.D. Thompson, 1.E.H. Wang, S.1. Wilson and N. Ganesalingam Thrombin-Mediated Events Implicated in Post-Thrombotic Recovery..................................................................................................... 253 J.W. Fenton II, F.A. Ofosu Anti-Tumor Effects of GBS Toxin Are Caused by Induction of a Targeted Inflammatory Reaction......... ... ... ... ... .... .... ..... .... ........ .... 265 e.G. Hellergvist, G. Thurman, B.A. Russell, D.L. Page, G.E. York, Y.F. Wang, e. Castillo and H.W. Sundell Biological Data and Docking Experiments of bFGF Sulfonated Distamycin A Derivative Complex ........................................................ 271 N. Mongelli and M. Grandi Clinical Ocular Angiogenesis.................................................................................. 277 D. BenEzra METHODOLOGY In Vivo Assays for Angiogenesis......................................................................... 283 W. Auerbach and R. Auerbach Quantitative Analysis of Extracellular Matrix Formation in Vivo and in Vitro ............................................................................. 291 E. Papadimitriou, B.R. Unsworth, M. E. Maragoudakis, and P.1. Lelkes ix Microvascular MOIphometry .............................................................................. 307 K. Narayan and C. Carcia The Corneal Model for the Study of Angiogenesis ....... ... ........ ... .... ...... ..... .... .... 315 D. Benezra Factitious Angiogenesis: Not So Factitious Anymore? The Role of Angiogenic Processes in the Endotheliali- zation of Artificial Cardiovascular Prostheses....................... .... ...... ...... 321 P.1. Lelkes, D.M. Chick, M.M. Samet, V. Nikolaychik, G.A. Thomas, R.L. Hammond, S. Isoda, and L.W. Stephenson ABSTRACTS ........................................................................................................... 333 PARTICIPANTS...................................................................................................... 359 INDEX..................................................................................................................... 369 x
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