Cancer Stem Cells (eBook)

Preface 5
Contents 8
List of Editors and Contributors 10
Editors 10
Contributors 10
Niche for Normal and Cancer Stem Cells 16
1 Introduction 17
2 The Melanocyte Stem Cell Serves as an IdealModel to Understand Quiescence of Stem Cells 18
3 Definition of MSC 19
4 Isolation of MSCs En Masse 20
5 Evaluation of Gene Function by MC- Specific Gene Manipulation 21
6 Induction of QuiescentMSCs RequiresMultiple Steps 22
7 A Working Hypothesis for the Induction of QuiescentMSCs 23
8 Induction of QuiescentMSCs In Vitro: Future Direction 25
References 27
c-Myc and Activated Ras During Skin Tumorigenesis: Cooperation at the Cancer Stem Cell Level? 28
1 The Myc Proto-oncogenes 29
2 Distinct Consequences of c-Myc Overexpression in Epidermal Cell Types 30
3 The Role of Endogenous c-Myc in the Epidermis 32
4 The Role of Endogenous c-Myc in Ras- Mediated Skin Tumorigenesis 33
5 c-Myc and RasMu Function in Epidermal Cancer Initiating Cells 34
References 37
Wnt Signaling in Stem Cells and Lung Cancer 42
1 Overview ofWnt Signaling 43
2 Stem Cells, Cancer Stem Cells, and Lung Cancer 46
3 Wnt Signaling in Stem Cell Maintenance and Regeneration 50
4 Wnt Signaling in Lung Cancer 52
5 Potential Therapeutic Approaches Targeting theWnt Pathway 59
6 Summary 61
References 62
Bone Morphogenetic Proteins Regulate Tumorigenicity in Human Glioblastoma Stem Cells 74
1 Materials and Methods 90
References 93
Strategies to Induce Nuclear Reprogramming 97
1 Introduction 98
2 Reprogramming by Nuclear Transfer 98
3 Reprogramming by Cell Fusion 101
4 Culture-Induced Reprogramming 103
5 Reprogramming by Defined Factors 105
6 Outlook 107
References 108
The Intestinal Stem Cell Niche Studied Through Conditional Transgenesis 113
1 Introduction 114
2 Stem Cells Within the Small Intestine 114
3 Analysis of Crypt Survival After Exposure to Ionising Radiation 115
4 Signalling Pathways Regulating Intestinal Homeostasis: TheWnt Signalling Pathway 116
5 Summary 119
References 120
The Migrating Cancer Stem Cells Model– A Conceptual Explanation of Malignant Tumour Progression 123
1 The Multistep CarcinogenesisModel and Tumour Heterogeneity 124
2 TheWnt/ß-Catenin Signalling Pathway 128
3 De-differentiated Tumour Cells at the Invasion Front Show Characteristics of Stemness 131
4 The Model of Migrating Tumour Stem Cells 132
References 134
Bone Marrow Niche and Leukemia 139
1 Stem Cells in Health and in Cancer 140
2 Significant Role of the Stem Cell Niche 141
3 Hematopoietic Stem Cells, Archetype of Adult Stem Cells 143
4 Divisional Kinetics and Genotyping for Identification of Stem Cells 143
5 Stem Cell Niche: The Importance of Being Connected 145
6 Affinity of HSC Toward Stromal Cells 146
7 Homotypic and Heterotypic Interactions 147
8 Significance of Adhesion Molecules for Regulation of Self- Renewal 148
9 Conclusion 149
References 150
Breast Stem Cells and Cancer 154
1 Introduction 154
2 Cancer Stem Cells 156
3 DCIS MammospheresÒImportance of EGF and Notch Signalling 160
References 163
Prostate Cancer Stem Cells: A Target for New Therapies 168
1 Introduction 169
2 TransgenicMouse Models of Prostate Cancer 170
3 Prostate Cancer: A Disease of Epithelial Differentiation 170
4 Stem cell Expansion In Vitro 171
5 Definition of the Stem Cell Phenotype in Prostate 172
6 The Origins of Prostate Cancer 174
7 Isolation of Prostate Cancer Stem Cells 176
8 Gene Expression in Prostate Cancer Stem Cells 180
9 Implications for Prostate Cancer Therapy 183
References 188
The Hedgehog Signaling Network, Mammary Stem Cells, and Breast Cancer: Connections and Controversies 193
1 Introduction 194
2 Stem and Progenitor Cells in Mammary Gland Ductal Development 197
3 The Hedgehog Signaling Network in Mammals 199
4 Expression and Function of Ï CanonicalÓ Hedgehog Network Genes During MouseMammary Ductal Development 201
5 The Ligands 202
6 The PTCH Receptors 203
7 The GLI Transcription Factors 206
8 AWorking Model for Hedgehog Network Regulation of Mammary Ductal Development 209
9 DoesActivated Hedgehog SignalingRegulateMammary Epithelial Stem Cell Self- Renewal or Maintenance? 211
10 Evidence for a Role of the Hedgehog Network in Mammary Cancer 215
11 Could Activated Hedgehog Signaling Regulate "Breast Cancer Stem Cells"? 218
12 Can Hedgehog Signaling Antagonists Be Used for the Treatment of Breast Cancer? 219
13 Concluding Remarks 220
References 221
Strategies to Eliminate Cancer Stem Cells 230
1 The Paradox of Response and Survival 230
2 The Dandelion Phenomenon 232
3 Eliminating Cancer Stem Cells 234
4 Conclusions 237
References 237
DNA Repair in Stem Cell Maintenance and Conversion to Cancer Stem Cells 242
1 Human Diseases Linked to Inherited Defects in DNA Repair Genes 243
2 Accelerated Stem Cell Aging After Significant DNA Damage 245
3 Robust Stem Cell Transplantation as a Marker of Stem Cell Maintenance 245
4 The Role of Mismatch Repair in Stem Cell Maintenance 247
5 Stem Cell Defects Due to Loss of Mismatch Repair 249
6 Current Studies of Genomic Instability During Stem Cell Aging and Malignant Transformation 251
7 Summary 252
References 253
Tumorigenic Epithelial Stem Cells and Their Normal Counterparts 256
1 Background 257
2 Results 258
3 Discussion 266
4 Methods 270
References 272