Cancer Stem Cells
Identification and Targets
Herausgegeben:Bapat, Sharmila A.
Cancer Stem Cells
Identification and Targets
Herausgegeben:Bapat, Sharmila A.
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A new frontier in the battle to understand and treat cancer
The identification of cancer stem cells (CSCs) has opened a new avenue for understanding cancer biology and how cancer should be treated. This book, the first dedicated to CSC research, introduces key concepts and discoveries, including: _ Detailed review of the regulatory mechanisms of cancer development and the transformation of CSCs to cancer cells _ Methods of isolation and characterization _ Latest therapeutic advances _ Recent findings in the study of CSCs and the status of current research _ Application of stem cell…mehr
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A new frontier in the battle to understand and treat cancer
The identification of cancer stem cells (CSCs) has opened a new avenue for understanding cancer biology and how cancer should be treated. This book, the first dedicated to CSC research, introduces key concepts and discoveries, including:
_ Detailed review of the regulatory mechanisms of cancer development and the transformation of CSCs to cancer cells
_ Methods of isolation and characterization
_ Latest therapeutic advances
_ Recent findings in the study of CSCs and the status of current research
_ Application of stem cell principles to cancer biology and the challenges of developing combination stem and cancer biology targets for therapeutics
In addition, the book examines specific types of cancers in which CSCs have been identified, including acute leukemias, retinoblastomas, melanomas, and breast, brain, ovarian, and prostate cancers.
Each chapter has been contributed by one or more pioneers in the field and carefully edited to ensure a thorough and uniform approach. Readers gain an insider's view of the authors' laboratories, research methods, and their results. References to the primary literature are provided at the end of each chapter.
As the first book in its field, Cancer Stem Cells is an invaluable repository of information for cancer biologists, stem cell researchers, and clinicians. It will serve as a springboard to understanding the mechanisms of CSCs and their potential for developing new, more effective therapeutics.
Hinweis: Dieser Artikel kann nur an eine deutsche Lieferadresse ausgeliefert werden.
The identification of cancer stem cells (CSCs) has opened a new avenue for understanding cancer biology and how cancer should be treated. This book, the first dedicated to CSC research, introduces key concepts and discoveries, including:
_ Detailed review of the regulatory mechanisms of cancer development and the transformation of CSCs to cancer cells
_ Methods of isolation and characterization
_ Latest therapeutic advances
_ Recent findings in the study of CSCs and the status of current research
_ Application of stem cell principles to cancer biology and the challenges of developing combination stem and cancer biology targets for therapeutics
In addition, the book examines specific types of cancers in which CSCs have been identified, including acute leukemias, retinoblastomas, melanomas, and breast, brain, ovarian, and prostate cancers.
Each chapter has been contributed by one or more pioneers in the field and carefully edited to ensure a thorough and uniform approach. Readers gain an insider's view of the authors' laboratories, research methods, and their results. References to the primary literature are provided at the end of each chapter.
As the first book in its field, Cancer Stem Cells is an invaluable repository of information for cancer biologists, stem cell researchers, and clinicians. It will serve as a springboard to understanding the mechanisms of CSCs and their potential for developing new, more effective therapeutics.
Hinweis: Dieser Artikel kann nur an eine deutsche Lieferadresse ausgeliefert werden.
Produktdetails
- Produktdetails
- Verlag: Wiley & Sons
- Artikelnr. des Verlages: 14512201000
- 1. Auflage
- Seitenzahl: 288
- Erscheinungstermin: 1. November 2008
- Englisch
- Abmessung: 240mm x 161mm x 19mm
- Gewicht: 522g
- ISBN-13: 9780470122013
- ISBN-10: 0470122013
- Artikelnr.: 25055386
- Herstellerkennzeichnung
- Libri GmbH
- Europaallee 1
- 36244 Bad Hersfeld
- 06621 890
- Verlag: Wiley & Sons
- Artikelnr. des Verlages: 14512201000
- 1. Auflage
- Seitenzahl: 288
- Erscheinungstermin: 1. November 2008
- Englisch
- Abmessung: 240mm x 161mm x 19mm
- Gewicht: 522g
- ISBN-13: 9780470122013
- ISBN-10: 0470122013
- Artikelnr.: 25055386
- Herstellerkennzeichnung
- Libri GmbH
- Europaallee 1
- 36244 Bad Hersfeld
- 06621 890
Sharmila Bapat, PHD, is a group leader of a small research group at the National Centre for Cell Science at India's University of Pune. She is an author of the first report on the isolation and identification of stem cells in ovarian cancer. Dr. Bapat organizes workshops on topics such as cell line establishment, immortalization of cultured cells, and stem cell protocols. She is also on the board of editors of the recently launched Journal of Ovarian Research.
Contributors xi
Preface xiii
1 Cancer Stem Cells: Similarities and Variations in the Theme of Normal
Stem Cells 1
Sharmila Bapat, Anne Collins, Michael Dean, Kenneth Nephew, and Suraiya
Rasheed
1.1 Introduction 1
1.2 Stem Cells in the Life of an Organism 2
1.2.1 Stem Cells in Early Development and Fetal Life 3
1.2.2 Stem Cells in the Adult Organism 4
1.3 Cancer Stem Cells 7
1.3.1 Activation of Stem Cells and Cancer 7
1.3.2 Isolation and Identification of Cancer Stem Cells 10
1.3.3 De Novo Generation of a New Organ (Tumor) by Transformed Stem Cells
12
1.4 Self-Renewal and Differentiation in CSCs 13
1.5 CSC Plasticity as Regulated by Intrinsic and Extrinsic Stem Cell
Factors 14
1.5.1 Stem Cell Intrinsic Factors: Genetic and Epigenetic Effects 14
1.5.2 Stem Cell Extrinsic Effects: Niche Effects and Microenvironmental
Signaling 16
1.6 Conclusions and Future Perspectives 18
References 20
2 Leukemic Stem Cells 27
Sharmila Bapat
2.1 Introduction 27
2.2 Dysregulation of Hematopoiesis in Leukemia 28
2.2.1 Normal Hematopoietic Stem Cell Hierarchies 28
2.2.2 Understanding Aberrant Hierarchies in Leukemia 30
2.2.3 Types of Leukemia 31
2.3 Identification and isolation of Cancer-Initiating Cells in Leukemia 35
2.4 Molecular Regulation of Aberrant Hierarchies 36
2.4.1 Signaling Pathways Deregulated in Leukemia 37
2.4.2 Self-Renewal of Normal and Leukemic Stem Cells 39
2.4.3 Epigenetic Effects 40
2.4.4 MicroRNA in Leukemia Development 42
2.5 Conclusions and Future Perspectives 44
References 45
3 Isolation and Characterization of Breast and Brain Cancer Stem Cells 57
Meera Saxena and Annapoorni Rangarajan
3.1 Introduction 57
3.2 Breast Cancer Stem Cells 58
3.2.1 Mammary Gland Architecture and Cell Types 58
3.2.2 Breast Cancer 59
3.2.3 Identification of Breast Cancer Stem Cells 59
3.2.4 Putative Breast Cancer Stem Cells that Exhibit the CD44+ CD24-/low
Lin- Marker Profile 61
3.2.5 ESA+ Subpopulation of CD24-low Lin- Cells Enriched by Tumorigenicity
61
3.2.6 Tumorigenic Breast Cells Displaying Properties of Stem Cells 61
3.2.7 In Vitro Propagation of Breast Cancer Stem Cells as Mammospheres 62
3.3 Brain Cancer Stem Cells 64
3.3.1 Brain Architecture and Cell Types 64
3.3.2 Brain Cancers 65
3.3.3 Brain Stem Cells 66
3.3.4 Brain Cancer Stem Cells 66
3.3.5 Brain Cancer-Derived Cells that Generate Tumor Spheres 67
3.4 Conclusions and Future Perspectives 69
References 70
4 Cancer Stem Cell Side Populations 73
Danuta Balicki and Raymond Beaulieu
4.1 Introduction 73
4.2 Stem Cell Side Populations 75
4.3 Side Populations in Normal Tissue 78
4.4 Side Populations in Tumors 79
4.5 Overcoming Side Population Limitations 80
4.6 Conclusions and Future Perspectives 81
References 82
5 Evidence for Cancer Stem Cells in Retinoblastoma 87
Gail M. Seigel
5.1 Introduction 87
5.2 Elusive Origins of Retinoblastoma 87
5.3 Sources of Retinoblastoma Cells for Study 88
5.4 Precedent for Cancer Stem Cells 88
5.5 Side Populations in Retinoblastoma 89
5.6 Immunoreactivity to Stem Cell Markers in Retinoblastoma 89
5.7 Conclusions and Future Perspectives 91
References 92
6 Ovarian Stem Cell Biology and the Emergence of Ovarian Cancer Stem Cells
95
Anjali Kusumbe and Sharmila Bapat
6.1 Introduction 95
6.2 Overview of the Human Ovary 95
6.2.1 Histological Landmarks 95
6.2.2 Ovarian Development: The Story Before Birth 96
6.2.3 The Mammalian Oogenesis Dogma 98
6.3 Stem/Progenitor Cells in the Adult Mammalian Ovary 98
6.3.1 Historical Perspective 98
6.3.2 The Oogenesis Dogma Revisited 99
6.4 Is Ovarian Cancer a Stem Cell Disease? 104
6.4.1 Putative Role of Stem/Progenitor Cells in Ovarian Cancer 104
6.4.2 Tumor as an Aberrant Organ Initiated by Cancer Stem Cells 105
6.4.3 Ovarian Cancer Stem Cells Isolated as a Side Population 106
6.4.4 New Challenge: Targeting Ovarian Cancer Stem Cells 106
References 107
7 Prostate Cancer Stem Cells 111
Stefanie Hager, Norman J. Maitland, and Anne Collins
7.1 Introduction 111
7.2 Human Prostate Biology Gland Architecture, and Pathological Alterations
111
7.3 Prostate Epithelial Stem Cells 113
7.3.1 Evidence for Prostate Epithelial Stem Cells 113
7.3.2 Isolation of Human Prostate Epithelial Stem Cells and Demonstration
of Their Stem Cell Character 116
7.3.3 Epithelial Stem Cells in the Murine Prostate 118
7.3.4 Other Markers of Prostate Epithelial Stem Cells 119
7.4 Prostate Cancer Stem Cells 120
7.4.1 Role of Stem Cells in Prostate Cancer 120
7.4.2 Prospective Isolation of Prostate Cancer Stem Cells from Human Tissue
Samples 122
7.4.3 Role of the Stem Cell Niche in Prostate Cancer 124
7.4.4 Putative Markers of Prostate Cancer Stem Cells 124
7.5 Stem Cell Tracking in the Prostate 125
7.6 Conclusions and Future Perspectives 127
References 127
8 Molecular Signatures of Highly Malignant Melanoma Stem Cells 135
Suraiya Rasheed
8.1 General Properties of Human Melanomas 135
8.2 Characteristics of Stem Cell-Derived Melanomas 136
8.3 The Cat Model System for Stem Cell Melanomas 137
8.3.1 Biological Characteristics of Highly Malignant Stem Cell Melanomas
138
8.3.2 Trans-differentiation of the Malignant Cat Melanoma into Neuronal
Cells 139
8.3.3 Proteins Associated with Neuronal Cell Differentiation 140
8.3.4 Cell Cycle Dysregulation and Antitumorigenic Effects During Cell
Differentiation 144
8.3.5 Molecular Signatures of Self Renewal and Long-Term Proliferation of
Tumor Cells 145
8.3.6 Proteins Involved in Tumorigenesis and Metastasis 147
8.3.7 Expression of Germline and Embryonic Proteins in Cat Melanomas 149
8.3.8 Naturally Occurring Protein-Protein Interaction Complexes in
Melanomas 149
8.3.9 Networks of Protein Interaction Pathways 152
8.4 Challenges of Research in Cancer Stem Cellsand Therapeutics 152
8.5 Conclusions and Future Perspectives 154
References 156
9 Invasion Program of Normal and Cancer Stem Cells 167
David Olmeda, Gema Moreno-Bueno, David Sarrió, José Palacios, and Amparo
Cano
9.1 Introduction 167
9.2 Basics of Tumor Progression: Invasion and Metastasis 168
9.3 Epithelial-to-Mesenchymal Transition in Development and Its Relation to
The Invasive Process 169
9.4 Regulation of EMT: From Signals to Molecular Pathways 172
9.5 EMT and Cancer Stem Cells 176
9.6 Can Stem Cell Properties Be Extensive to Invasive Tumor Cells? 177
9.7 Is There a Unique EMT Program Linked to Invasion? 178
9.8 Evidence of EMT in Human Clinical Tumors 180
9.9 Expression of Mesenchymal Markers and Cadherin Switching in Carcinomas
181
9.10 Expression of EMT Inducers in Human Tumors 183
9.11 Occurrence of EMT in a Specific Subset of Breast Carcinomas 185
9.12 Conclusions and Future Perspectives 186 References 187
10 Epigenetics in Cancer Stem Cell Development 197
Kenneth Nephew, Curt Balch, Tim H.-M. Huang, Zhang Shu, Michael Chan, and
Pearlly Yan
10.1 Introduction 197
10.2 Characterization of Candidate Cancer Stem Cells 198
10.3 Possible Origins of Cancer Stem Cells 198
10.4 Epigenetics in Normal Development 199
10.5 Epigenetic Regulation of the Cancer Stem Cell Phenotype 200
10.6 Contributions of Epigenetics to Drug Resistance in Cancer Stem Cells
204
10.7 Genome-Wide Interrogation of Epigenetic Modifications in Cancer Stem
Cells 206
10.8 Epigenetic Therapies Against Poorly Differentiated Cancer Cells 207
10.9 Conclusions and Future Perspectives 208
References 209
11 Cancer Stem Cells and New Therapeutic Approaches 217
Michael Dean
11.1 Cancer Stem Cells 217
11.2 Activation of Stem Cells and Cancer 218
11.2.1 Initiation and Promotion Revised 219
11.2.2 Stem Cell Activation and Specific Cancers 221
11.3 Major Cancers and Risk Factors 223
11.3.1 Liver Cancer 223
11.3.2 Lung Cancer 224
11.3.3 Gastric Cancer 224
11.3.4 Pancreatic Cancer 224
11.3.5 Cervical Cancer 225
11.4 Treatment Implications 225
11.5 Future Perspectives 227
11.6 Conclusions 228
References 243
12 Immunobiology of Cancer Stem Cells 233
Shubhada V. Chiplunkar
12.1 Cancer Stem Cells 233
12.2 Cancer Stem Cells and Lymphocytes 234
12.3 Trafficking of Normal Stem Cells and Metastasis of Cancer Stem Cells
236
References 238
Index 243
Preface xiii
1 Cancer Stem Cells: Similarities and Variations in the Theme of Normal
Stem Cells 1
Sharmila Bapat, Anne Collins, Michael Dean, Kenneth Nephew, and Suraiya
Rasheed
1.1 Introduction 1
1.2 Stem Cells in the Life of an Organism 2
1.2.1 Stem Cells in Early Development and Fetal Life 3
1.2.2 Stem Cells in the Adult Organism 4
1.3 Cancer Stem Cells 7
1.3.1 Activation of Stem Cells and Cancer 7
1.3.2 Isolation and Identification of Cancer Stem Cells 10
1.3.3 De Novo Generation of a New Organ (Tumor) by Transformed Stem Cells
12
1.4 Self-Renewal and Differentiation in CSCs 13
1.5 CSC Plasticity as Regulated by Intrinsic and Extrinsic Stem Cell
Factors 14
1.5.1 Stem Cell Intrinsic Factors: Genetic and Epigenetic Effects 14
1.5.2 Stem Cell Extrinsic Effects: Niche Effects and Microenvironmental
Signaling 16
1.6 Conclusions and Future Perspectives 18
References 20
2 Leukemic Stem Cells 27
Sharmila Bapat
2.1 Introduction 27
2.2 Dysregulation of Hematopoiesis in Leukemia 28
2.2.1 Normal Hematopoietic Stem Cell Hierarchies 28
2.2.2 Understanding Aberrant Hierarchies in Leukemia 30
2.2.3 Types of Leukemia 31
2.3 Identification and isolation of Cancer-Initiating Cells in Leukemia 35
2.4 Molecular Regulation of Aberrant Hierarchies 36
2.4.1 Signaling Pathways Deregulated in Leukemia 37
2.4.2 Self-Renewal of Normal and Leukemic Stem Cells 39
2.4.3 Epigenetic Effects 40
2.4.4 MicroRNA in Leukemia Development 42
2.5 Conclusions and Future Perspectives 44
References 45
3 Isolation and Characterization of Breast and Brain Cancer Stem Cells 57
Meera Saxena and Annapoorni Rangarajan
3.1 Introduction 57
3.2 Breast Cancer Stem Cells 58
3.2.1 Mammary Gland Architecture and Cell Types 58
3.2.2 Breast Cancer 59
3.2.3 Identification of Breast Cancer Stem Cells 59
3.2.4 Putative Breast Cancer Stem Cells that Exhibit the CD44+ CD24-/low
Lin- Marker Profile 61
3.2.5 ESA+ Subpopulation of CD24-low Lin- Cells Enriched by Tumorigenicity
61
3.2.6 Tumorigenic Breast Cells Displaying Properties of Stem Cells 61
3.2.7 In Vitro Propagation of Breast Cancer Stem Cells as Mammospheres 62
3.3 Brain Cancer Stem Cells 64
3.3.1 Brain Architecture and Cell Types 64
3.3.2 Brain Cancers 65
3.3.3 Brain Stem Cells 66
3.3.4 Brain Cancer Stem Cells 66
3.3.5 Brain Cancer-Derived Cells that Generate Tumor Spheres 67
3.4 Conclusions and Future Perspectives 69
References 70
4 Cancer Stem Cell Side Populations 73
Danuta Balicki and Raymond Beaulieu
4.1 Introduction 73
4.2 Stem Cell Side Populations 75
4.3 Side Populations in Normal Tissue 78
4.4 Side Populations in Tumors 79
4.5 Overcoming Side Population Limitations 80
4.6 Conclusions and Future Perspectives 81
References 82
5 Evidence for Cancer Stem Cells in Retinoblastoma 87
Gail M. Seigel
5.1 Introduction 87
5.2 Elusive Origins of Retinoblastoma 87
5.3 Sources of Retinoblastoma Cells for Study 88
5.4 Precedent for Cancer Stem Cells 88
5.5 Side Populations in Retinoblastoma 89
5.6 Immunoreactivity to Stem Cell Markers in Retinoblastoma 89
5.7 Conclusions and Future Perspectives 91
References 92
6 Ovarian Stem Cell Biology and the Emergence of Ovarian Cancer Stem Cells
95
Anjali Kusumbe and Sharmila Bapat
6.1 Introduction 95
6.2 Overview of the Human Ovary 95
6.2.1 Histological Landmarks 95
6.2.2 Ovarian Development: The Story Before Birth 96
6.2.3 The Mammalian Oogenesis Dogma 98
6.3 Stem/Progenitor Cells in the Adult Mammalian Ovary 98
6.3.1 Historical Perspective 98
6.3.2 The Oogenesis Dogma Revisited 99
6.4 Is Ovarian Cancer a Stem Cell Disease? 104
6.4.1 Putative Role of Stem/Progenitor Cells in Ovarian Cancer 104
6.4.2 Tumor as an Aberrant Organ Initiated by Cancer Stem Cells 105
6.4.3 Ovarian Cancer Stem Cells Isolated as a Side Population 106
6.4.4 New Challenge: Targeting Ovarian Cancer Stem Cells 106
References 107
7 Prostate Cancer Stem Cells 111
Stefanie Hager, Norman J. Maitland, and Anne Collins
7.1 Introduction 111
7.2 Human Prostate Biology Gland Architecture, and Pathological Alterations
111
7.3 Prostate Epithelial Stem Cells 113
7.3.1 Evidence for Prostate Epithelial Stem Cells 113
7.3.2 Isolation of Human Prostate Epithelial Stem Cells and Demonstration
of Their Stem Cell Character 116
7.3.3 Epithelial Stem Cells in the Murine Prostate 118
7.3.4 Other Markers of Prostate Epithelial Stem Cells 119
7.4 Prostate Cancer Stem Cells 120
7.4.1 Role of Stem Cells in Prostate Cancer 120
7.4.2 Prospective Isolation of Prostate Cancer Stem Cells from Human Tissue
Samples 122
7.4.3 Role of the Stem Cell Niche in Prostate Cancer 124
7.4.4 Putative Markers of Prostate Cancer Stem Cells 124
7.5 Stem Cell Tracking in the Prostate 125
7.6 Conclusions and Future Perspectives 127
References 127
8 Molecular Signatures of Highly Malignant Melanoma Stem Cells 135
Suraiya Rasheed
8.1 General Properties of Human Melanomas 135
8.2 Characteristics of Stem Cell-Derived Melanomas 136
8.3 The Cat Model System for Stem Cell Melanomas 137
8.3.1 Biological Characteristics of Highly Malignant Stem Cell Melanomas
138
8.3.2 Trans-differentiation of the Malignant Cat Melanoma into Neuronal
Cells 139
8.3.3 Proteins Associated with Neuronal Cell Differentiation 140
8.3.4 Cell Cycle Dysregulation and Antitumorigenic Effects During Cell
Differentiation 144
8.3.5 Molecular Signatures of Self Renewal and Long-Term Proliferation of
Tumor Cells 145
8.3.6 Proteins Involved in Tumorigenesis and Metastasis 147
8.3.7 Expression of Germline and Embryonic Proteins in Cat Melanomas 149
8.3.8 Naturally Occurring Protein-Protein Interaction Complexes in
Melanomas 149
8.3.9 Networks of Protein Interaction Pathways 152
8.4 Challenges of Research in Cancer Stem Cellsand Therapeutics 152
8.5 Conclusions and Future Perspectives 154
References 156
9 Invasion Program of Normal and Cancer Stem Cells 167
David Olmeda, Gema Moreno-Bueno, David Sarrió, José Palacios, and Amparo
Cano
9.1 Introduction 167
9.2 Basics of Tumor Progression: Invasion and Metastasis 168
9.3 Epithelial-to-Mesenchymal Transition in Development and Its Relation to
The Invasive Process 169
9.4 Regulation of EMT: From Signals to Molecular Pathways 172
9.5 EMT and Cancer Stem Cells 176
9.6 Can Stem Cell Properties Be Extensive to Invasive Tumor Cells? 177
9.7 Is There a Unique EMT Program Linked to Invasion? 178
9.8 Evidence of EMT in Human Clinical Tumors 180
9.9 Expression of Mesenchymal Markers and Cadherin Switching in Carcinomas
181
9.10 Expression of EMT Inducers in Human Tumors 183
9.11 Occurrence of EMT in a Specific Subset of Breast Carcinomas 185
9.12 Conclusions and Future Perspectives 186 References 187
10 Epigenetics in Cancer Stem Cell Development 197
Kenneth Nephew, Curt Balch, Tim H.-M. Huang, Zhang Shu, Michael Chan, and
Pearlly Yan
10.1 Introduction 197
10.2 Characterization of Candidate Cancer Stem Cells 198
10.3 Possible Origins of Cancer Stem Cells 198
10.4 Epigenetics in Normal Development 199
10.5 Epigenetic Regulation of the Cancer Stem Cell Phenotype 200
10.6 Contributions of Epigenetics to Drug Resistance in Cancer Stem Cells
204
10.7 Genome-Wide Interrogation of Epigenetic Modifications in Cancer Stem
Cells 206
10.8 Epigenetic Therapies Against Poorly Differentiated Cancer Cells 207
10.9 Conclusions and Future Perspectives 208
References 209
11 Cancer Stem Cells and New Therapeutic Approaches 217
Michael Dean
11.1 Cancer Stem Cells 217
11.2 Activation of Stem Cells and Cancer 218
11.2.1 Initiation and Promotion Revised 219
11.2.2 Stem Cell Activation and Specific Cancers 221
11.3 Major Cancers and Risk Factors 223
11.3.1 Liver Cancer 223
11.3.2 Lung Cancer 224
11.3.3 Gastric Cancer 224
11.3.4 Pancreatic Cancer 224
11.3.5 Cervical Cancer 225
11.4 Treatment Implications 225
11.5 Future Perspectives 227
11.6 Conclusions 228
References 243
12 Immunobiology of Cancer Stem Cells 233
Shubhada V. Chiplunkar
12.1 Cancer Stem Cells 233
12.2 Cancer Stem Cells and Lymphocytes 234
12.3 Trafficking of Normal Stem Cells and Metastasis of Cancer Stem Cells
236
References 238
Index 243
Contributors xi
Preface xiii
1 Cancer Stem Cells: Similarities and Variations in the Theme of Normal
Stem Cells 1
Sharmila Bapat, Anne Collins, Michael Dean, Kenneth Nephew, and Suraiya
Rasheed
1.1 Introduction 1
1.2 Stem Cells in the Life of an Organism 2
1.2.1 Stem Cells in Early Development and Fetal Life 3
1.2.2 Stem Cells in the Adult Organism 4
1.3 Cancer Stem Cells 7
1.3.1 Activation of Stem Cells and Cancer 7
1.3.2 Isolation and Identification of Cancer Stem Cells 10
1.3.3 De Novo Generation of a New Organ (Tumor) by Transformed Stem Cells
12
1.4 Self-Renewal and Differentiation in CSCs 13
1.5 CSC Plasticity as Regulated by Intrinsic and Extrinsic Stem Cell
Factors 14
1.5.1 Stem Cell Intrinsic Factors: Genetic and Epigenetic Effects 14
1.5.2 Stem Cell Extrinsic Effects: Niche Effects and Microenvironmental
Signaling 16
1.6 Conclusions and Future Perspectives 18
References 20
2 Leukemic Stem Cells 27
Sharmila Bapat
2.1 Introduction 27
2.2 Dysregulation of Hematopoiesis in Leukemia 28
2.2.1 Normal Hematopoietic Stem Cell Hierarchies 28
2.2.2 Understanding Aberrant Hierarchies in Leukemia 30
2.2.3 Types of Leukemia 31
2.3 Identification and isolation of Cancer-Initiating Cells in Leukemia 35
2.4 Molecular Regulation of Aberrant Hierarchies 36
2.4.1 Signaling Pathways Deregulated in Leukemia 37
2.4.2 Self-Renewal of Normal and Leukemic Stem Cells 39
2.4.3 Epigenetic Effects 40
2.4.4 MicroRNA in Leukemia Development 42
2.5 Conclusions and Future Perspectives 44
References 45
3 Isolation and Characterization of Breast and Brain Cancer Stem Cells 57
Meera Saxena and Annapoorni Rangarajan
3.1 Introduction 57
3.2 Breast Cancer Stem Cells 58
3.2.1 Mammary Gland Architecture and Cell Types 58
3.2.2 Breast Cancer 59
3.2.3 Identification of Breast Cancer Stem Cells 59
3.2.4 Putative Breast Cancer Stem Cells that Exhibit the CD44+ CD24-/low
Lin- Marker Profile 61
3.2.5 ESA+ Subpopulation of CD24-low Lin- Cells Enriched by Tumorigenicity
61
3.2.6 Tumorigenic Breast Cells Displaying Properties of Stem Cells 61
3.2.7 In Vitro Propagation of Breast Cancer Stem Cells as Mammospheres 62
3.3 Brain Cancer Stem Cells 64
3.3.1 Brain Architecture and Cell Types 64
3.3.2 Brain Cancers 65
3.3.3 Brain Stem Cells 66
3.3.4 Brain Cancer Stem Cells 66
3.3.5 Brain Cancer-Derived Cells that Generate Tumor Spheres 67
3.4 Conclusions and Future Perspectives 69
References 70
4 Cancer Stem Cell Side Populations 73
Danuta Balicki and Raymond Beaulieu
4.1 Introduction 73
4.2 Stem Cell Side Populations 75
4.3 Side Populations in Normal Tissue 78
4.4 Side Populations in Tumors 79
4.5 Overcoming Side Population Limitations 80
4.6 Conclusions and Future Perspectives 81
References 82
5 Evidence for Cancer Stem Cells in Retinoblastoma 87
Gail M. Seigel
5.1 Introduction 87
5.2 Elusive Origins of Retinoblastoma 87
5.3 Sources of Retinoblastoma Cells for Study 88
5.4 Precedent for Cancer Stem Cells 88
5.5 Side Populations in Retinoblastoma 89
5.6 Immunoreactivity to Stem Cell Markers in Retinoblastoma 89
5.7 Conclusions and Future Perspectives 91
References 92
6 Ovarian Stem Cell Biology and the Emergence of Ovarian Cancer Stem Cells
95
Anjali Kusumbe and Sharmila Bapat
6.1 Introduction 95
6.2 Overview of the Human Ovary 95
6.2.1 Histological Landmarks 95
6.2.2 Ovarian Development: The Story Before Birth 96
6.2.3 The Mammalian Oogenesis Dogma 98
6.3 Stem/Progenitor Cells in the Adult Mammalian Ovary 98
6.3.1 Historical Perspective 98
6.3.2 The Oogenesis Dogma Revisited 99
6.4 Is Ovarian Cancer a Stem Cell Disease? 104
6.4.1 Putative Role of Stem/Progenitor Cells in Ovarian Cancer 104
6.4.2 Tumor as an Aberrant Organ Initiated by Cancer Stem Cells 105
6.4.3 Ovarian Cancer Stem Cells Isolated as a Side Population 106
6.4.4 New Challenge: Targeting Ovarian Cancer Stem Cells 106
References 107
7 Prostate Cancer Stem Cells 111
Stefanie Hager, Norman J. Maitland, and Anne Collins
7.1 Introduction 111
7.2 Human Prostate Biology Gland Architecture, and Pathological Alterations
111
7.3 Prostate Epithelial Stem Cells 113
7.3.1 Evidence for Prostate Epithelial Stem Cells 113
7.3.2 Isolation of Human Prostate Epithelial Stem Cells and Demonstration
of Their Stem Cell Character 116
7.3.3 Epithelial Stem Cells in the Murine Prostate 118
7.3.4 Other Markers of Prostate Epithelial Stem Cells 119
7.4 Prostate Cancer Stem Cells 120
7.4.1 Role of Stem Cells in Prostate Cancer 120
7.4.2 Prospective Isolation of Prostate Cancer Stem Cells from Human Tissue
Samples 122
7.4.3 Role of the Stem Cell Niche in Prostate Cancer 124
7.4.4 Putative Markers of Prostate Cancer Stem Cells 124
7.5 Stem Cell Tracking in the Prostate 125
7.6 Conclusions and Future Perspectives 127
References 127
8 Molecular Signatures of Highly Malignant Melanoma Stem Cells 135
Suraiya Rasheed
8.1 General Properties of Human Melanomas 135
8.2 Characteristics of Stem Cell-Derived Melanomas 136
8.3 The Cat Model System for Stem Cell Melanomas 137
8.3.1 Biological Characteristics of Highly Malignant Stem Cell Melanomas
138
8.3.2 Trans-differentiation of the Malignant Cat Melanoma into Neuronal
Cells 139
8.3.3 Proteins Associated with Neuronal Cell Differentiation 140
8.3.4 Cell Cycle Dysregulation and Antitumorigenic Effects During Cell
Differentiation 144
8.3.5 Molecular Signatures of Self Renewal and Long-Term Proliferation of
Tumor Cells 145
8.3.6 Proteins Involved in Tumorigenesis and Metastasis 147
8.3.7 Expression of Germline and Embryonic Proteins in Cat Melanomas 149
8.3.8 Naturally Occurring Protein-Protein Interaction Complexes in
Melanomas 149
8.3.9 Networks of Protein Interaction Pathways 152
8.4 Challenges of Research in Cancer Stem Cellsand Therapeutics 152
8.5 Conclusions and Future Perspectives 154
References 156
9 Invasion Program of Normal and Cancer Stem Cells 167
David Olmeda, Gema Moreno-Bueno, David Sarrió, José Palacios, and Amparo
Cano
9.1 Introduction 167
9.2 Basics of Tumor Progression: Invasion and Metastasis 168
9.3 Epithelial-to-Mesenchymal Transition in Development and Its Relation to
The Invasive Process 169
9.4 Regulation of EMT: From Signals to Molecular Pathways 172
9.5 EMT and Cancer Stem Cells 176
9.6 Can Stem Cell Properties Be Extensive to Invasive Tumor Cells? 177
9.7 Is There a Unique EMT Program Linked to Invasion? 178
9.8 Evidence of EMT in Human Clinical Tumors 180
9.9 Expression of Mesenchymal Markers and Cadherin Switching in Carcinomas
181
9.10 Expression of EMT Inducers in Human Tumors 183
9.11 Occurrence of EMT in a Specific Subset of Breast Carcinomas 185
9.12 Conclusions and Future Perspectives 186 References 187
10 Epigenetics in Cancer Stem Cell Development 197
Kenneth Nephew, Curt Balch, Tim H.-M. Huang, Zhang Shu, Michael Chan, and
Pearlly Yan
10.1 Introduction 197
10.2 Characterization of Candidate Cancer Stem Cells 198
10.3 Possible Origins of Cancer Stem Cells 198
10.4 Epigenetics in Normal Development 199
10.5 Epigenetic Regulation of the Cancer Stem Cell Phenotype 200
10.6 Contributions of Epigenetics to Drug Resistance in Cancer Stem Cells
204
10.7 Genome-Wide Interrogation of Epigenetic Modifications in Cancer Stem
Cells 206
10.8 Epigenetic Therapies Against Poorly Differentiated Cancer Cells 207
10.9 Conclusions and Future Perspectives 208
References 209
11 Cancer Stem Cells and New Therapeutic Approaches 217
Michael Dean
11.1 Cancer Stem Cells 217
11.2 Activation of Stem Cells and Cancer 218
11.2.1 Initiation and Promotion Revised 219
11.2.2 Stem Cell Activation and Specific Cancers 221
11.3 Major Cancers and Risk Factors 223
11.3.1 Liver Cancer 223
11.3.2 Lung Cancer 224
11.3.3 Gastric Cancer 224
11.3.4 Pancreatic Cancer 224
11.3.5 Cervical Cancer 225
11.4 Treatment Implications 225
11.5 Future Perspectives 227
11.6 Conclusions 228
References 243
12 Immunobiology of Cancer Stem Cells 233
Shubhada V. Chiplunkar
12.1 Cancer Stem Cells 233
12.2 Cancer Stem Cells and Lymphocytes 234
12.3 Trafficking of Normal Stem Cells and Metastasis of Cancer Stem Cells
236
References 238
Index 243
Preface xiii
1 Cancer Stem Cells: Similarities and Variations in the Theme of Normal
Stem Cells 1
Sharmila Bapat, Anne Collins, Michael Dean, Kenneth Nephew, and Suraiya
Rasheed
1.1 Introduction 1
1.2 Stem Cells in the Life of an Organism 2
1.2.1 Stem Cells in Early Development and Fetal Life 3
1.2.2 Stem Cells in the Adult Organism 4
1.3 Cancer Stem Cells 7
1.3.1 Activation of Stem Cells and Cancer 7
1.3.2 Isolation and Identification of Cancer Stem Cells 10
1.3.3 De Novo Generation of a New Organ (Tumor) by Transformed Stem Cells
12
1.4 Self-Renewal and Differentiation in CSCs 13
1.5 CSC Plasticity as Regulated by Intrinsic and Extrinsic Stem Cell
Factors 14
1.5.1 Stem Cell Intrinsic Factors: Genetic and Epigenetic Effects 14
1.5.2 Stem Cell Extrinsic Effects: Niche Effects and Microenvironmental
Signaling 16
1.6 Conclusions and Future Perspectives 18
References 20
2 Leukemic Stem Cells 27
Sharmila Bapat
2.1 Introduction 27
2.2 Dysregulation of Hematopoiesis in Leukemia 28
2.2.1 Normal Hematopoietic Stem Cell Hierarchies 28
2.2.2 Understanding Aberrant Hierarchies in Leukemia 30
2.2.3 Types of Leukemia 31
2.3 Identification and isolation of Cancer-Initiating Cells in Leukemia 35
2.4 Molecular Regulation of Aberrant Hierarchies 36
2.4.1 Signaling Pathways Deregulated in Leukemia 37
2.4.2 Self-Renewal of Normal and Leukemic Stem Cells 39
2.4.3 Epigenetic Effects 40
2.4.4 MicroRNA in Leukemia Development 42
2.5 Conclusions and Future Perspectives 44
References 45
3 Isolation and Characterization of Breast and Brain Cancer Stem Cells 57
Meera Saxena and Annapoorni Rangarajan
3.1 Introduction 57
3.2 Breast Cancer Stem Cells 58
3.2.1 Mammary Gland Architecture and Cell Types 58
3.2.2 Breast Cancer 59
3.2.3 Identification of Breast Cancer Stem Cells 59
3.2.4 Putative Breast Cancer Stem Cells that Exhibit the CD44+ CD24-/low
Lin- Marker Profile 61
3.2.5 ESA+ Subpopulation of CD24-low Lin- Cells Enriched by Tumorigenicity
61
3.2.6 Tumorigenic Breast Cells Displaying Properties of Stem Cells 61
3.2.7 In Vitro Propagation of Breast Cancer Stem Cells as Mammospheres 62
3.3 Brain Cancer Stem Cells 64
3.3.1 Brain Architecture and Cell Types 64
3.3.2 Brain Cancers 65
3.3.3 Brain Stem Cells 66
3.3.4 Brain Cancer Stem Cells 66
3.3.5 Brain Cancer-Derived Cells that Generate Tumor Spheres 67
3.4 Conclusions and Future Perspectives 69
References 70
4 Cancer Stem Cell Side Populations 73
Danuta Balicki and Raymond Beaulieu
4.1 Introduction 73
4.2 Stem Cell Side Populations 75
4.3 Side Populations in Normal Tissue 78
4.4 Side Populations in Tumors 79
4.5 Overcoming Side Population Limitations 80
4.6 Conclusions and Future Perspectives 81
References 82
5 Evidence for Cancer Stem Cells in Retinoblastoma 87
Gail M. Seigel
5.1 Introduction 87
5.2 Elusive Origins of Retinoblastoma 87
5.3 Sources of Retinoblastoma Cells for Study 88
5.4 Precedent for Cancer Stem Cells 88
5.5 Side Populations in Retinoblastoma 89
5.6 Immunoreactivity to Stem Cell Markers in Retinoblastoma 89
5.7 Conclusions and Future Perspectives 91
References 92
6 Ovarian Stem Cell Biology and the Emergence of Ovarian Cancer Stem Cells
95
Anjali Kusumbe and Sharmila Bapat
6.1 Introduction 95
6.2 Overview of the Human Ovary 95
6.2.1 Histological Landmarks 95
6.2.2 Ovarian Development: The Story Before Birth 96
6.2.3 The Mammalian Oogenesis Dogma 98
6.3 Stem/Progenitor Cells in the Adult Mammalian Ovary 98
6.3.1 Historical Perspective 98
6.3.2 The Oogenesis Dogma Revisited 99
6.4 Is Ovarian Cancer a Stem Cell Disease? 104
6.4.1 Putative Role of Stem/Progenitor Cells in Ovarian Cancer 104
6.4.2 Tumor as an Aberrant Organ Initiated by Cancer Stem Cells 105
6.4.3 Ovarian Cancer Stem Cells Isolated as a Side Population 106
6.4.4 New Challenge: Targeting Ovarian Cancer Stem Cells 106
References 107
7 Prostate Cancer Stem Cells 111
Stefanie Hager, Norman J. Maitland, and Anne Collins
7.1 Introduction 111
7.2 Human Prostate Biology Gland Architecture, and Pathological Alterations
111
7.3 Prostate Epithelial Stem Cells 113
7.3.1 Evidence for Prostate Epithelial Stem Cells 113
7.3.2 Isolation of Human Prostate Epithelial Stem Cells and Demonstration
of Their Stem Cell Character 116
7.3.3 Epithelial Stem Cells in the Murine Prostate 118
7.3.4 Other Markers of Prostate Epithelial Stem Cells 119
7.4 Prostate Cancer Stem Cells 120
7.4.1 Role of Stem Cells in Prostate Cancer 120
7.4.2 Prospective Isolation of Prostate Cancer Stem Cells from Human Tissue
Samples 122
7.4.3 Role of the Stem Cell Niche in Prostate Cancer 124
7.4.4 Putative Markers of Prostate Cancer Stem Cells 124
7.5 Stem Cell Tracking in the Prostate 125
7.6 Conclusions and Future Perspectives 127
References 127
8 Molecular Signatures of Highly Malignant Melanoma Stem Cells 135
Suraiya Rasheed
8.1 General Properties of Human Melanomas 135
8.2 Characteristics of Stem Cell-Derived Melanomas 136
8.3 The Cat Model System for Stem Cell Melanomas 137
8.3.1 Biological Characteristics of Highly Malignant Stem Cell Melanomas
138
8.3.2 Trans-differentiation of the Malignant Cat Melanoma into Neuronal
Cells 139
8.3.3 Proteins Associated with Neuronal Cell Differentiation 140
8.3.4 Cell Cycle Dysregulation and Antitumorigenic Effects During Cell
Differentiation 144
8.3.5 Molecular Signatures of Self Renewal and Long-Term Proliferation of
Tumor Cells 145
8.3.6 Proteins Involved in Tumorigenesis and Metastasis 147
8.3.7 Expression of Germline and Embryonic Proteins in Cat Melanomas 149
8.3.8 Naturally Occurring Protein-Protein Interaction Complexes in
Melanomas 149
8.3.9 Networks of Protein Interaction Pathways 152
8.4 Challenges of Research in Cancer Stem Cellsand Therapeutics 152
8.5 Conclusions and Future Perspectives 154
References 156
9 Invasion Program of Normal and Cancer Stem Cells 167
David Olmeda, Gema Moreno-Bueno, David Sarrió, José Palacios, and Amparo
Cano
9.1 Introduction 167
9.2 Basics of Tumor Progression: Invasion and Metastasis 168
9.3 Epithelial-to-Mesenchymal Transition in Development and Its Relation to
The Invasive Process 169
9.4 Regulation of EMT: From Signals to Molecular Pathways 172
9.5 EMT and Cancer Stem Cells 176
9.6 Can Stem Cell Properties Be Extensive to Invasive Tumor Cells? 177
9.7 Is There a Unique EMT Program Linked to Invasion? 178
9.8 Evidence of EMT in Human Clinical Tumors 180
9.9 Expression of Mesenchymal Markers and Cadherin Switching in Carcinomas
181
9.10 Expression of EMT Inducers in Human Tumors 183
9.11 Occurrence of EMT in a Specific Subset of Breast Carcinomas 185
9.12 Conclusions and Future Perspectives 186 References 187
10 Epigenetics in Cancer Stem Cell Development 197
Kenneth Nephew, Curt Balch, Tim H.-M. Huang, Zhang Shu, Michael Chan, and
Pearlly Yan
10.1 Introduction 197
10.2 Characterization of Candidate Cancer Stem Cells 198
10.3 Possible Origins of Cancer Stem Cells 198
10.4 Epigenetics in Normal Development 199
10.5 Epigenetic Regulation of the Cancer Stem Cell Phenotype 200
10.6 Contributions of Epigenetics to Drug Resistance in Cancer Stem Cells
204
10.7 Genome-Wide Interrogation of Epigenetic Modifications in Cancer Stem
Cells 206
10.8 Epigenetic Therapies Against Poorly Differentiated Cancer Cells 207
10.9 Conclusions and Future Perspectives 208
References 209
11 Cancer Stem Cells and New Therapeutic Approaches 217
Michael Dean
11.1 Cancer Stem Cells 217
11.2 Activation of Stem Cells and Cancer 218
11.2.1 Initiation and Promotion Revised 219
11.2.2 Stem Cell Activation and Specific Cancers 221
11.3 Major Cancers and Risk Factors 223
11.3.1 Liver Cancer 223
11.3.2 Lung Cancer 224
11.3.3 Gastric Cancer 224
11.3.4 Pancreatic Cancer 224
11.3.5 Cervical Cancer 225
11.4 Treatment Implications 225
11.5 Future Perspectives 227
11.6 Conclusions 228
References 243
12 Immunobiology of Cancer Stem Cells 233
Shubhada V. Chiplunkar
12.1 Cancer Stem Cells 233
12.2 Cancer Stem Cells and Lymphocytes 234
12.3 Trafficking of Normal Stem Cells and Metastasis of Cancer Stem Cells
236
References 238
Index 243