Stem Cell Biology and Regenerative Medicine

Series EditorKursad Turksen, Ph.D.kturksen@ohri.ca

For further volumes:http://www.springer.com/series/7896

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Alison L. AllanEditor

Cancer Stem Cells in Solid Tumors

EditorAlison L. Allan Depts. of Oncology and Anat. & Cell BiologySchulich School of Med. and Dent.University of Western OntarioLondon, Ontario, Canadaalison.allan@lhsc.on.ca

ISBN 978-1-61779-245-8 e-ISBN 978-1-61779-246-5DOI 10.1007/978-1-61779-246-5Springer New York Dordrecht Heidelberg London

Library of Congress Control Number: 2011932988

© Springer Science+Business Media, LLC 2011All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Humana Press, c/o Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden.The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights.

Printed on acid-free paper

Humana Press is part of Springer Science+Business Media (www.springer.com)

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Preface

Recently, there has been increasing support for the “cancer stem cell” hypothesis, which postulates that cancer arises from a subpopulation of tumor-initiating cells or cancer stem cells (CSCs). There are currently two conflicting views that attempt to explain tumor formation. The classical stochastic model suggests that every cell within a tumor is a potential tumor-initiator, but that entry into the cell cycle is governed by a low probability of stochastic mutations. According to this model, it would be impossible to tell which cell initiated the tumor since each cell has an equal ability to be malignant. By contrast, the hierarchy theory (upon which the CSC hypothesis is based) proposes that only a subset of cells within a tumor is capable of initiating tumor growth, but that these cells all do so at a high frequency. According to this theory, it should be possible to identify and target the cells responsible for tumor initiation and progression because not all cells have the same phenotypic and func-tional characteristics.

While the idea of CSCs has been around for more than 100 years, evidence from the hematology field has now demonstrated the critical role of stem cells in hemato-logical malignancies and suggested that these same mechanisms could also be cen-tral to the initiation, progression, and treatment of solid cancers. Indeed, several pivotal studies have recently provided compelling evidence that these cells do exist in solid tumors of many types including breast, brain, colorectal, pancreas, prostate, melanoma, lung, ovarian, liver, and head and neck cancer. Furthermore, clinical and experimental studies have demonstrated that CSCs exhibit many classical properties of normal stem cells, including a high self-renewal capacity and the ability to gener-ate heterogeneous lineages; the requirement for a specific “niche”/microenvironment to grow; and an increased capacity for self-protection against harsh environments, toxins, and drugs.

This multi-authored volume focuses specifically on the role of CSCs in solid cancers. The authors are all active investigators with research programs related to oncology and/or stem cell biology, and are leaders in their field. Part I (Chap. 1) serves to introduce the concept of CSCs vs. normal stem cells, including a histori-cal perspective and the contributing lessons from leukemia. Part II (Chaps. 2–11) describes the identification and role of CSCs in various forms of solid cancer,

vi Preface

organized according to disease site. Part III (Chaps. 12–14) elaborates on molecular pathways that are involved in driving CSC function, with a particular focus on the convergence of embryonic and tumorigenic signaling pathways. Part IV (Chaps. 15–18) describes available model systems and modalities for studying CSC biol-ogy and therapeutic development, including in vitro and in vivo model systems and assays and imaging modalities. Part V (Chaps. 19–23) discusses the importance of CSCs for cancer management and treatment, including implications for prognosis, prediction, and treatment resistance. Finally, Part VI (Chap. 24) provides the con-cluding thoughts for the book, including consideration of the controversy sur-rounding the CSC hypothesis. The editor and the authors hope that this work will provide a comprehensive overview of this evolving and important field.

London, ON Alison L. AllanCanada

vii

Acknowledgments

I would like to express my gratitude to all of the authors for their scholarly efforts in summarizing the current literature in this rapidly evolving field. I would also like to thank Mindy Okura-Marszycki and Kursad Turksen for giving me the opportunity to edit this book, and acknowledge Vindra Dass and Renata Hutter for all of their help throughout the editorial and publication process. Finally, I am grateful to mem-bers of my own research group for their patience, contributions, helpful discussion, and continued hard work in this exciting area of research.

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Contents

Part I Introduction to Cancer Stem Cells

1 Cancer Stem Cells: Historical Perspectives and Lessons from Leukemia ................................................................. 3Christopher R. Cogle

Part II Cancer Stem Cells in Solid Tumors

2 Cancer Stem Cells in Breast Cancer .................................................... 15Jenny E. Chu and Alison L. Allan

3 Cancer Stem Cells in Brain Cancer ..................................................... 37Xin Wang, Chitra Venugopal, and Sheila K. Singh

4 Cancer Stem Cells in Colorectal Cancer.............................................. 57Mauro Biffoni, Eros Fabrizi, and Lucia Ricci-Vitiani

5 Cancer Stem Cells in Pancreatic Cancer ............................................. 79Jorge Dorado, Alicia G. Serrano, and Christopher Heeschen

6 Cancer Stem Cells in Prostate Cancer ................................................. 99Paula Kroon, Davide Pellacani, Fiona M. Frame, Norman J. Maitland, and Anne T. Collins

7 Cancer Stem Cells in Melanoma .......................................................... 117Ping Jin, Qiuzhen Liu, Marianna Sabatino, David F. Stroncek, Francesco M. Marincola, and Ena Wang

8 Cancer Stem Cells in Lung Cancer ...................................................... 139Jun Shen and Feng Jiang

9 Cancer Stem Cells in Ovarian Cancer ................................................. 151Fang Fang, Curt Balch, Meng Li, Jay M. Pilrose, and Kenneth P. Nephew

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10 Cancer Stem Cells in Hepatocellular Cancer ...................................... 177Russell C. Langan and Itzhak Avital

11 Cancer Stem Cells in Head and Neck Cancer ..................................... 197Mark E.P. Prince and Samantha J. Davis

Part III Cancer Stem Cell Gene Expression and Mechanisms: Convergence of Embryonic and Tumorigenic Signaling Pathways

12 Relationship Between Regulatory Pathways in Pluripotent Stem Cells and Human Tumors ................................... 209Olga Gaidarenko and Yang Xu

13 Influence of the Embryonic Microenvironment on Tumor Progression ............................................................................ 223Daniela Quail, Meghan Taylor, Michael Jewer, and Lynne-Marie Postovit

14 The Epithelial-to-Mesenchymal Transition and Cancer Stem Cells ........................................................................... 243Jonas Fuxe

Part IV Model Systems for Studying Cancer Stem Cell Biology and Therapeutic Development

15 Application of Stem Cell Assays for the Characterization of Cancer Stem Cells .............................................................................. 259Pamela M. Willan and Gillian Farnie

16 Zebrafish as a Model to Study Stem Cells in Development, Disease, and Cancer .................................................. 283Viviana Anelli, Cristina Santoriello, and Marina C. Mione

17 Imaging Cancer Stem Cells ................................................................... 297Paula Foster

18 Mouse Models for Studying Normal and Cancer Stem Cells ............ 311David A. Hess

Part V Clinical and Therapeutic Implications of Cancer Stem Cells

19 Cancer Stem Cells and Disease Prognosis ........................................... 329Zeshaan A. Rasheed, Jeanne Kowalski, and William H. Matsui

20 Mechanisms of Radioresistance in Cancer Stem Cells ....................... 345Cleo Y-F Lee and Maximilian Diehn

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21 The Role of ABC Transporters in Cancer Stem Cell Drug Resistance ...................................................................................... 361Vera S. Donnenberg, Ludovic Zimmerlin, and Albert D. Donnenberg

22 Resistance to Endocrine Therapy in Breast Cancer: Are Breast Cancer Stem Cells Implicated? ......................................... 381Ciara S. O’Brien, Sacha J. Howell, Gillian Farnie, and Robert B. Clarke

23 Future Directions: Cancer Stem Cells as Therapeutic Targets .......................................................................... 403Alysha K. Croker and Alison L. Allan

Part VI Final Thoughts

24 Final Thoughts: Complexity and Controversy Surrounding the “Cancer Stem Cell” Paradigm ....................................................... 433Craig Gedye, Richard P. Hill, and Laurie Ailles

Index ................................................................................................................ 465

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Contributors

Laurie Ailles Ontario Cancer Institute, Campbell Family Institute of Cancer Research; and Departments of Medical Biophysics, University of Toronto, Toronto, ON, Canada

Alison L. Allan Departments of Oncology and Anatomy & Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada

London Regional Cancer Program, London Health Sciences Centre, London, ON, Canada

Viviana Anelli IFOM, The FIRC Institute of Molecular Oncology, Milan, Italy

Itzhak Avital National Cancer Institute (NIH), Surgery Branch, Bethesda, MD, USA

Curt Balch Medical Sciences Program, Indiana University, Bloomington, IN, USA

Indiana University Simon Cancer Center, Indianapolis, IN, USA

Mauro Biffoni Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy

Jenny E. Chu Department of Anatomy & Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada

Robert B. Clarke Breast Biology Group, School of Cancer and Enabling Sciences, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK

Christopher R. Cogle Department of Medicine, Division of Hematology/ Oncology, University of Florida, Gainesville, FL, USA

Program in Stem Cell Biology and Regenerative Medicine, University of Florida, Gainesville, FL, USA

xiv Contributors

Anne T. Collins Cancer Research Unit, Department of Biology, University of York, York, UK

Alysha K. Croker Department of Anatomy & Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada

Samantha J. Davis Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA

Maximilian Diehn Stanford Cancer Center, CA, USA

Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford, CA, USA

Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA

Albert D. Donnenberg Department of Medicine, Division of Hematology/ Oncology, University of Pittsburgh Cancer Institute and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Vera S. Donnenberg Department of Cardiovascular Surgery, Division of Hematology/Oncology, University of Pittsburgh Cancer Institute and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Jorge Dorado Clinical Research Programme, Stem Cells & Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain

Eros Fabrizi Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy

Fang Fang Medical Sciences Program, Indiana University, Bloomington, IN, USA

Gillian Farnie Cancer Stem Cell Research, University of Manchester, School of Cancer and Enabling Sciences, Paterson Institute for Cancer Research, Manchester, UK

Paula Foster Robarts Research Institute, London, ON, Canada

Department of Medical Biophysics, University of Western Ontario, London, ON, Canada

Fiona M. Frame Cancer Research Unit, Department of Biology, University of York, York, UK

Jonas Fuxe Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden

Olga Gaidarenko Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA

xvContributors

Craig Gedye Ontario Cancer Institute, Campbell Family Institute of Cancer Research, Toronto, ON, Canada

Christopher Heeschen Clinical Research Programme, Stem Cells & Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain

David A. Hess Department of Physiology & Pharmacology, The University of Western Ontario, London, ON, Canada

Vascular Biology Group, Krembil Centre for Stem Cell Biology, Robarts Research Institute, London, ON, Canada

Richard P. Hill Ontario Cancer Institute, Campbell Family Institute of Cancer Research, Departments of Medical Biophysics and Radiation Oncology, University of Toronto, Toronto, ON, Canada

Sacha J. Howell Department of Medical Oncology, The Christie NHS Foundation Trust, University of Manchester, Manchester, UK

Michael Jewer Department of Anatomy & Cell Biology, University of Western Ontario, London, ON, Canada

Feng Jiang Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA

Ping Jin Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA

Jeanne Kowalski Winship Cancer Institute, Emory University, Atlanta, GA, USA

Paula Kroon Cancer Research Unit, Department of Biology, University of York, York, UK

Russell C. Langan Surgery Branch, National Cancer Institute, National Institute of Health, Bethesda, MD, USA

Cleo Y-F Lee Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA, USA

Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA

Meng Li Medical Sciences Program, Indiana University, Bloomington, IN, USA

Qiuzhen Liu Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA

Norman J. Maitland Cancer Research Unit, Department of Biology, University of York, York, UK

Francesco M. Marincola Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA

xvi Contributors

William H. Matsui The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Marina C. Mione IFOM, The FIRC Institute of Molecular Oncology, Milan, Italy

Kenneth P. Nephew Medical Sciences Program, Indiana University, Bloomington, IN, USA

Indiana University Simon Cancer Center, Indianapolis, IN, USA

Ciara S. O’Brien Department of Medical Oncology, The Christie NHS Foundation Trust, University of Manchester, Manchester, UK

Davide Pellacani Cancer Research Unit, Department of Biology, University of York, York, UK

Jay M. Pilrose Medical Sciences Program, Indiana University, Bloomington, IN, USA

Lynne-Marie Postovit Department of Anatomy & Cell Biology, University of Western Ontario, London, ON, Canada

Mark E.P. Prince Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA

Daniela Quail Department of Anatomy & Cell Biology, University of Western Ontario, London, ON, Canada

Zeshaan A. Rasheed The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Lucia Ricci-Vitiani Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy

Marianna Sabatino Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA

Cristina Santoriello IFOM, The FIRC Institute of Molecular Oncology, Milan, Italy

Alicia G. Serrano Clinical Research Programme, Stem Cells & Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain

Jun Shen Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA

Sheila K. Singh McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, Canada

Departments of Surgery, Biochemistry & Biomedical Sciences, and Neuroscience, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada

xviiContributors

David F. Stroncek Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA

Meghan Taylor Department of Anatomy & Cell Biology, University of Western Ontario, London, ON, Canada

Chitra Venugopal McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, Canada

Ena Wang Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA

Xin Wang McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, Canada

Pamela M. Willan Cancer Stem Cell Research, University of Manchester, School of Cancer and Enabling Sciences, Paterson Institute for Cancer Research, Manchester, UK

Yang Xu Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA

Ludovic Zimmerlin Department of Cardiovascular Surgery, Division of Hematology/Oncology, University of Pittsburgh Cancer Institute Pittsburgh, Pittsburgh, PA, USA

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