Emerging Concepts of Tumor Exosome Mediated Cell Cell Communication
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1 Emerging Concepts of Tumor Exosome Mediated Cell Cell Communication
2 Huang-Ge Zhang Editor Emerging Concepts of Tumor Exosome Mediated Cell Cell Communication 2123
3 Editor Huang-Ge Zhang University of Louisville Louisville, KY USA ISBN ISBN (ebook) DOI / Springer New York Dordrecht Heidelberg London Library of Congress Control Number: Springer Science+Business Media New York 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (
4 Preface Over the past decades, secretion of proteins that bind to receptors on neighboring cells was considered a primary mode for communication between cells. Recently, the release of membrane vesicles including exosomes/microvesicles has become recognized as an important mode of intercellular communication. Unlike a single soluble factor secreted by cells, exosomes can carry a group of functional molecules enriched with particular proteins, lipids, and micrornas (mirnas) and provide an increased stability of the transported molecules. Therefore, exosomes can serve as intercellular communicators not only locally but also systemically. Exosomes are released by many different cell types, and their biological effects on the recipient cells are dependent on the composition of the exosomes and the microenvironment where the recipient cells are residents. This book will focus on exosomes as they relate to tumor cells and cancer. The first four chapters will cover the basic biology of exosomes and the roles of specific components of exosomes, primarily focusing on proteins, mrnas/mirna, and lipids. In the first chapter, Dr. Graça Raposo provides an introduction to exosomes, describes the composition, biogenesis, function of exosomes in general, and the methodology for isolation and characterization of exosomes/microvesicles. Chapter 2 written by Dr. Jan Lötvall further elucidates the role of exosomal shuttle RNA in cell-to-cell communication. Dr. Lötvall s group discovered that mirnas are encapsulated in exosomes and that they play a critical role in cell-cell communication and also as potential markers for prodiagnosis of diseases. Dr. Michel Record wrote Chapter 3 and he focuses on the effects of exosomal lipids in cell-cell communication. Development of cutting-edge lipidomic technology has provided a means to recognize the biological and pathobiological effects of lipids on many different cell types and diseases. Exosomes carrying lipids can function in exosomal lipid mediated targeting as well as carrying lipids to recipient cells. The final chapter in this section by Dr. Margot Zöller will cover the mechanisms underlying the selective recruitment of molecules into exosomes. Dr. Zöller uses tetraspanin as an excellent example to demonstrate how tetraspanins regulate protein assembly of exosomes and the possible recruitment of mirna. Book Chapters 5 9 focus on the effects of exosomes at the cellular and molecular levels, on tumor cell proliferation, on metastasis, and on immunosuppression. Topics in these chapters deal with the role of tumor exosomes in the progression of tumor development (Drs. Huang-Ge Zhang, William Grizzle, and Douglas Taylor); v
5 vi Preface the mechanisms underlying tumor exosome-mediated immunosuppression including induction of regulatory T cells and myeloid cells, immune modulation of T cells, and natural killer cells by tumor-derived exosomes (Dr. Theresa Whiteside), tumorstroma interactions (Dr. Johan K. O. Skog), and microenvironment regulation of metastasis by exosomes (Dr. David Lyden). The final chapter deals with the future of exosome biology and more specifically the induction of stem cells in regenerative medicine (Dr. Mariusz Ratajczak). There are many individuals I wish to thank, without whose efforts this book would not have become a reality. First and foremost, my thanks go to all the authors who contributed material for publication in this book. Their expertise and scientifically informed viewpoints, coupled with a collaborative spirit under tight time constrains, has made working with them a pleasure. I also wish to thank our acquisitions editor, Fiona Sarne for her patience, encouragement, and support. This book marked a lot of firsts for me, so in the process of learning the ins and outs of publishing a book of this nature, I also developed a very strong friendship with her. I look forward to working with her again in the future. Last, but not least, I thank my wife Lifeng Zhang, and my twin daughters Shuangqin Zhang and Shuangyin Zhang for their support and understanding during the many times that book-writing took precedence over family matters.
6 Contents 1 The Cell Biology of Exosomes: Historical and Perspectives... 1 Alessandra Lo Cicero and Graça Raposo 2 The Role of Exosomal Shuttle RNA (esrna) in Cell-to-Cell Communication Cecilia Lässer, Maria Eldh and Jan Lötvall 3 Exosomal Lipids in Cell Cell Communication Michel Record 4 The Functional Importance of Tetraspanins in Exosomes Sanyukta Rana and Margot Zöller 5 The Effects of Exosomes and Related Vesicles on Cancer Development, Progression, and Dissemination Huang-Ge Zhang and William E. Grizzle 6 Circulating Cell-derived Vesicles Mediate Tumor Progression Douglas D. Taylor and Cicek Gercel-Taylor 7 Immune Modulation of T Cells and Natural Killer Cells by Tumor-Derived Exosomes Theresa L. Whiteside 8 The Role of Tumor Exosomes in Tumorigenicity Johan K. O. Skog 9 Microenvironmental Regulation of Metastasis by Exosomes Haiying Zhang, Guillermo Garcia-Santos, Héctor Peinado and David C. Lyden 10 Microvesicles and Their Emerging Role in Cellular Therapies for Organ and Tissue Regeneration Mariusz Z. Ratajczak, Kasia Mierzejewska, Magda Kucia, Nick Greco and Janina Ratajczak Index vii
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