Stem Cells and Cancer (eBook)

Rebecca G. Bagley, Beverly A. Teicher (Herausgeber)

eBook Download: PDF

2009 | 2009
XVI, 346 Seiten
Humana Press (Verlag)
978-1-60327-933-8 (ISBN)

Infos

Significance of Stem Cells to Tumor Development

Cancer stem cells remain a controversial topic and the criteria that define cancer stem cells are continuing to evolve. A recent surge in stem cell research has ignited a field of discovery into many human diseases including diabetes, neuropathologies, and cancer. By replacing specific differentiated cells that have either been lost or died, stem cell therapy proves to be a very promising approach to the treatment of many debilitating diseases. Though stem cells may provide therapeutic benefit under certain conditions, they are also often implicated in the initiation, progression, and therapeutic resistance of malignant disease.

This first edition of Stem Cells and Cancer is intended to give a current perspective on the role of stem cells in cancer and strategies for novel therapies directed toward tumor stem cells. The current cancer stem cell hypothesis is presented in several chapters with distinctions made between the hierarchical and stochastic models of tumor cell development. 'Stemness,' self-renewal, pluripotency, clonality, and tumorigenicity are important concepts applied towards defining cancer stem cells. Signaling pathways such as Wnt, Sonic Hedgehog, Notch, and Bmi-1 that are involved in differentiation, proliferation, and survival are implicated in the malignant process. Additional chapters address the identification of cancer stem cell populations through the evaluation of molecular markers such as CD133, CD44, and CD24, for example, or by Hoescht dye exclusion to recognize 'side populations.' Mesenchymal and hematopoietic stem cells are described as well as mouse models that are employed to elucidate the properties and functionality of stem cells in cancer and the stem cell niche. This book encompasses a wide variety of human cancers that include but are not limited to leukemia, gliomas, breast, and prostate cancers. Resistance to conventional therapies, genetic versus epigenetic changes that affect therapeutic response and strategies to prevent disease recurrence are challenges have been incorporated into this volume. Stem Cells and Cancer represents a compendium of cutting edge research by experts in the field and will be instrumental in the study of this intriguing line of investigation for many years to come.

Rebecca Bagley is a senior scientist at Genzyme Corporation and has worked in the biotechnology industry for 20 years with degrees in biology from Wellesley College and Harvard University. Her expertise in drug development spans a wide range of approaches including immunotherapies,  gene and protein therapies, and small molecule delivery with publications in journals such as Molecular Cancer Therapeutics, Cancer Research, and Microvascular Research . Her current research focuses on stem cells, tumor vasculature, and target validation.

Dr. Beverly A. Teicher is Vice President of Oncology Research at Genzyme Corporation. Dr. Teicher completed a PhD in Bioorganic Chemistry at the Johns Hopkins University and postdoctoral training at Yale University School of Medicine. Dr. Teicher joined Dana-Farber Cancer Institute as an Assistant Professor of Pathology and rose to Associate Professor of Medicine and Radiation Therapy, Harvard Medical School at Dana-Farber Cancer Institute and Joint Center for Radiation Therapy. Dr. Teicher is an active member of the international scientific community having authored or co-authored more than 400 scientific publications. She has edited eight books, is senior editor for the journal Clinical Cancer Research and is series editor for the Cancer Drug Discovery and Development book series.

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Significance of Stem Cells to Tumor DevelopmentCancer stem cells remain a controversial topic and the criteria that define cancer stem cells are continuing to evolve. A recent surge in stem cell research has ignited a field of discovery into many human diseases including diabetes, neuropathologies, and cancer. By replacing specific differentiated cells that have either been lost or died, stem cell therapy proves to be a very promising approach to the treatment of many debilitating diseases. Though stem cells may provide therapeutic benefit under certain conditions, they are also often implicated in the initiation, progression, and therapeutic resistance of malignant disease. This first edition of Stem Cells and Cancer is intended to give a current perspective on the role of stem cells in cancer and strategies for novel therapies directed toward tumor stem cells. The current cancer stem cell hypothesis is presented in several chapters with distinctions made between the hierarchical and stochastic models of tumor cell development. "e;Stemness,"e; self-renewal, pluripotency, clonality, and tumorigenicity are important concepts applied towards defining cancer stem cells. Signaling pathways such as Wnt, Sonic Hedgehog, Notch, and Bmi-1 that are involved in differentiation, proliferation, and survival are implicated in the malignant process. Additional chapters address the identification of cancer stem cell populations through the evaluation of molecular markers such as CD133, CD44, and CD24, for example, or by Hoescht dye exclusion to recognize side populations. Mesenchymal and hematopoietic stem cells are described as well as mouse models that are employed to elucidate the properties and functionality of stem cells in cancer and the stem cell niche. This book encompasses a wide variety of human cancers that include but are not limited to leukemia, gliomas, breast, and prostate cancers. Resistance to conventionaltherapies, genetic versus epigenetic changes that affect therapeutic response and strategies to prevent disease recurrence are challenges have been incorporated into this volume. Stem Cells and Cancer represents a compendium of cutting edge research by experts in the field and will be instrumental in the study of this intriguing line of investigation for many years to come.Rebecca Bagley is a senior scientist at Genzyme Corporation and has worked in the biotechnology industry for 20 years with degrees in biology from Wellesley College and Harvard University. Her expertise in drug development spans a wide range of approaches including immunotherapies,  gene and protein therapies, and small molecule delivery with publications in journals such as Molecular Cancer Therapeutics, Cancer Research, and Microvascular Research . Her current research focuses on stem cells, tumor vasculature, and target validation.Dr. Beverly A. Teicher is Vice President of Oncology Research at Genzyme Corporation. Dr. Teicher completed a PhD in Bioorganic Chemistry at the Johns Hopkins University and postdoctoral training at Yale University School of Medicine. Dr. Teicher joined Dana-Farber Cancer Institute as an Assistant Professor of Pathology and rose to Associate Professor of Medicine and Radiation Therapy, Harvard Medical School at Dana-Farber Cancer Institute and Joint Center for Radiation Therapy. Dr. Teicher is an active member of the international scientific community having authored or co-authored more than 400 scientific publications. She has edited eight books, is senior editor for the journal Clinical Cancer Research and is series editor for the Cancer Drug Discovery and Development book series.

Inhalt

Preface 5
Contents 6
Contributors 9
Introduction to Cancer Stem Cells 14
The Cancer Stem Cell Hypothesis 15
THE CANCER STEM CELL MODEL OF CARCINOGENESIS 15
WHERE DO CANCER STEM CELLS COME FROM? 18
OPEN QUESTIONS: LIMITATIONS OF THE EXPERIMENTAL EVIDENCE 20
CLINICAL IMPLICATIONS: TARGETING CANCER STEM CELLS FOR THERAPY 22
CONCLUSIONS 24
REFERENCES 24
Tumor Stem Cells and Malignant Cells, One and the Same 27
INTRODUCTION 27
EARLY OBSERVATIONS 28
TUMOR CELL HETEROGENEITY 30
HEMATOPOIESIS AS A MODEL 31
METASTASIS 32
CARCINOGENESIS 34
CONCLUSIONS 35
REFERENCES 36
The Stem Cell Niche 39
Mesenchymal Stem Cells in Tumor Stroma 40
INTRODUCTION 40
MESENCHYMAL STEM CELLS 42
TUMOR STROMAGENESIS 42
TUMOR-ASSOCIATED FIBROBLASTS 42
THERAPEUTIC POTENTIAL OF MESENCHYMAL STEM CELLS 43
A THERAPEUTIC “DOUBLE-EDGED SWORD” 44
CONCLUSIONS 44
REFERENCES 45
Molecular Pathways and Gene Expression 48
Wnt Signaling in Cancer: From Embryogenesis to Stem Cell Self-Renewal 49
EMBRYOGENESIS AND ITS REQUIREMENTS 49
WNT SIGNAL TRANSDUCTION 50
CROSS-TALK BETWEEN WNT AND OTHER SIGNAL TRANSDUCTION PATHWAYS DURING EMBRYOGENESIS AND CANCER 53
WNT, NICHES, STEM CELLS, AND THEIR FATES 56
WNT IN STEM CELL HOMEOSTASIS AND REGENERATION 58
STEM CELLS AND CANCER 58
CONCLUSIONS: WNT: FROM EMBRYOGENESIS TO STEM CELL FATE AND CANCER 60
ACKNOWLEDGMENT 61
REFERENCES 61
PTEN in Hematopoietic and Intestinal Stem Cells and Cancer 68
INTRODUCTION 68
THE PTEN/PI3K/AKT SIGNALING PATHWAY 69
PTEN, HSCS, AND CANCER 71
PTEN, ISCS, AND CANCER 74
CONCLUDING REMARKS 77
REFERENCES 79
Transcription Factors in Cancer Stem Cells of the Hematopoietic Lineage 83
LEUKEMIC STEM CELLS 83
ROLE OF TRANSCRIPTION FACTORS IN NORMAL HEMATOPOIESIS 84
EFFECTS OF TRANSCRIPTION FACTORS IN NORMAL HEMATOPOIETIC STEM CELLS 85
ROLE OF TRANSCRIPTION FACTORS IN HUMAN LEUKEMIA 85
PU.1 DEREGULATION TRANSFORMS HEMATOPOIETIC STEM CELLS 86
CEBPA 87
OTHER TRANSCRIPTION FACTORS 89
REFERENCES 89
Stem Cell Chromatin Patterns and DNA Hypermethylation 92
THE EPIGENETIC TOOL BOX 92
EPIGENETIC CHANGES DURING NORMAL DEVELOPMENT 94
PROGENITOR CELLS AS TUMOR INITIATING CELLS 97
EPIGENETIC CHANGES DURING TUMOR INITIATION AND MALIGNANT PROGRESSION 98
POLYCOMB REPRESSIVE COMPLEXES: AN EPIGENETIC BRIDGE BETWEEN NORMAL AND MALIGNANT DEVELOPMENT? 100
REFERENCES 102
Plasticity Underlying Multipotent Tumor Stem Cells 105
THE STEM-CELL-LIKE NATURE OF CANCER 105
NODAL SIGNALING AND CELL FATE 107
NODAL AS A MEDIATOR AND BIOMARKER OF TUMOR PROGRESSION 110
REGULATION OF NODAL EXPRESSION: CONVERGENCE WITH NOTCH 112
EPIGENETIC REPROGRAMMING OF MULTIPOTENT TUMOR CELLS 113
REFERENCES 116
Cancer Stem Cells in Solid Tumors 119
Glioma Stem Cells in the Context of Oncogenesis 120
GLIOMAS CONTAIN HETEROGENEOUS TUMOR CELL POPULATIONS ACCORDING TO MORPHOLOGICAL CRITERIA 120
EVIDENCE FOR THE EXISTENCE OF GLIOMA STEM CELLS 122
GLIOMA STEM CELLS IN THE CONTEXT OF GLIOMA ONCOGENESIS 124
CLINICAL IMPLICATIONS OF GLIOMA STEM CELLS 127
CONCLUDING REMARKS 128
REFERENCES 128
Mouse Mammary Tumor Virus: Stem Cells and Mammary Cancer 132
INTRODUCTION 132
STEM/PROGENITOR CELL ACTIVITY IN MMTV-INDUCED TUMORS 133
STEM/PROGENITOR CELL HIERARCHY 135
SELECTIVE DNA SEGREGATION 137
ASYMMETRIC VERSUS SYMMETRIC CELL DIVISION IN CANCER 141
STEM/PROGENITOR CELLS ARE TARGETS FOR MMTV TRANSFORMATION 142
CONCLUSIONS 143
REFERENCES 143
Tumor Dormancy, Metastasis, and Cancer Stem Cells 146
INTRODUCTION 146
METASTASIS AND DORMANCY 147
THE CSC HYPOTHESIS 148
STEM CELLS, CANCER STEM CELLS, AND METASTATIC CELLS 150
THERAPEUTIC IMPLICATIONS 154
CONCLUDING REMARKS 154
ACKNOWLEDGMENTS 155
REFERENCES 155
Cancer Stem Cells: Gastrointestinal Cancers 159
INTRODUCTION 159
CANCER GENOMICS AND BIOLOGY IN GASTROINTESTINAL CANCERS 159
COLORECTAL CANCER 162
HEPATOCELLULAR CARCINOMA 164
ESOPHAGEAL AND STOMACH CANCER 164
PERSPECTIVE 165
REFERENCES 165
Cancer Stem Cells: Hepatocellular Carcinoma 168
INTRODUCTION 168
A STEM CELL ORIGIN OF LIVER TUMORS 169
LIVER CANCER STEM CELLS 171
CONCLUSION 175
REFERENCES 175
Cancer Stem Cells: Lung Cancer 179
ACKNOWLEDGMENTS 184
REFERENCES 184
Cancer Stem Cells: Pancreatic Cancer 187
PANCREATIC CANCER OVERVIEW 187
SIGNALING PATHWAYS CONTROLLING PANCREATIC CANCER DEVELOPMENT 188
ISOLATION OF PANCREATIC CANCER STEM CELLS 190
ALTERNATIVE CSC MARKERS? 191
IN VITRO CULTURE OF PANCREATIC CANCER STEM CELLS 192
PATHWAYS INVOLVED IN CONTROLLING PANCREATIC CSC FUNCTION 193
PANCREATIC CANCER STEM CELLS AND METASTASIS 194
PANCREATIC CANCER STEM CELLS AND RESISTANCE TO THERAPY 195
CANCER STEM CELL-BASED THERAPEUTICS 196
CONCLUSION 197
REFERENCES 197
Prostate Stem Cells and Cancer in Animals 200
INTRODUCTION 200
GROWTH ASSAYS FOR STEM CELLS FROM THE NORMAL PROSTATE 202
A PLACE CALLED HOME: STEM CELL LOCALIZATION AND NICHE 203
SEARCHING FOR THE INVISIBLE: ENRICHING FOR PROSTATIC PROGENITOR CELLS VIA STEM CELL MARKERS 205
MODELS OF DIFFERENTIATION 206
SEARCHING FOR PROSTATE CANCER STEM CELLS: MODEL SYSTEMS AND PROSPECTS 208
CONCLUSION 212
ACKNOWLEDGMENTS 213
REFERENCES 213
Prostate Cancer Stem/Progenitor Cells 218
INTRODUCTION 218
CELLULAR ORGANIZATION OF THE PROSTATIC GLAND 219
NORMAL HUMAN PROSTATE STEM/PROGENITOR CELLS 220
STEM-LIKE CELLS IN TUMORS AND PCa STEM/PROGENITOR CELLS 222
ACKNOWLEDGMENTS 228
BIBLIOGRAPHY 228
Adult Prostate Epithelium Renewal, Stem Cells and Cancer 232
INTRODUCTION 232
THE ADULT PROSTATE GLAND 233
DEVELOPMENT OF THE PROSTATE 233
PROSTATE EPITHELIUM HOMEOSTASIS 236
PROSTATE STEM CELL ASSAYS 238
ISOLATION OF PROSTATE STEM CELLS 240
PROSTATE STEM CELLS AND CANCER 241
CONCLUSIONS 242
REFERENCES 243
Stem Cells, Angiogenesis, and Neurogenesis in Tumors 248
INTRODUCTION 248
SIMILARITIES BETWEEN TUMOR ANGIOGENESIS AND INNERVATION 249
NEUROTROPHIC FACTORS THAT PROMOTE ANGIOGENESIS 249
ANGIOGENIC FACTORS THAT PROMOTE NEURONAL OUTGROWTH 250
BONE-MARROW-DERIVED STEM CELLS IN TUMORS 250
CONCLUSIONS 251
REFERENCES 251
Targeting Cancer Stem Cells with Therapy 254
Implications of Cancer Stem Cells for Cancer Therapy 255
INTRODUCTION 255
CSC AND PRECANCEROUS LESIONS: CLINICAL IMPLICATIONS 256
CSC AND MESENCHYMAL STEM CELLS 257
RADIATION AND DRUG RESISTANCE OF CSC 257
CSC AND CANCER RELAPSE 258
CSC AND CANCER METASTASIS 258
CSC AND PROGNOSIS 258
THERAPEUTICS TARGETING CSC 258
SURFACE MOLECULE TARGETING THERAPY 259
ONCOPROTEIN TARGETING THERAPY 259
STEM CELL REGULATION PATHWAY TARGETING 260
DRUG AND RADIATION RESISTANCE INHIBITORS 260
MESENCHYMAL STEM CELLS AND ANTI-NICHE CSC THERAPY 260
CONCLUSIONS 261
REFERENCES 261
Targeting Leukemic Stem Cells 263
BACKGROUND 263
HEMATOPOIETIC AND LEUKEMIC STEM CELLS: COMMONALITIES AND DIFFERENCES 264
LEUKEMIC STEM CELL TYPES 264
TARGETS IN LSCS 266
CONCLUSIONS AND FUTURE PERSPECTIVES 271
ACKNOWLEDGMENTS 272
REFERENCES 272
Targeting Brain Cancer Stem Cells in the Clinic 274
IDENTIFICATION AND ISOLATION OF BRAIN CANCER STEM CELLS 274
CANCER STEM CELLS IN THERAPEUTIC RESISTANCE 276
CANCER STEM CELLS IN PROGNOSIS 277
DIFFERENTIATION THERAPY 278
TARGETING SIGNAL TRANSDUCTION PATHWAYS OF CANCER STEM CELLS 278
TARGETING CANCER STEM CELLS USING ACTIVE IMMUNOTHERAPY 279
TARGETING CANCER STEM CELLS WITH PASSIVE IMMUNOTHERAPY 281
SUMMARY 282
REFERENCES 282
Critical Roles of Tumorigenic and Migrating Cancer Stem/ Progenitor Cells in Cancer Progression and their Therapeutic Implications 286
INTRODUCTION 286
FUNCTIONS OF TUMORIGENIC AND MIGRATING CANCER STEM/ PROGENITOR CELLS IN CANCER PROGRESSION AND METASTASES 288
NEW CONCEPT ON HETEROGENEITY OF CANCERS DERIVED FROM DISTINCT TUMORIGENIC AND MIGRATING CANCER STEM/ PROGENITOR CELLS 293
NOVEL THERAPIES AGAINST AGGRESSIVE AND RECURRENT CANCERS 295
CONCLUSIONS AND FUTURE RESEARCH 298
ACKNOWLEDGMENTS 298
REFERENCES 299
Therapeutic Index and the Cancer Stem Cell Paradigm 308
INTRODUCTION 308
TUMOR HETEROGENEITY AND THE IDENTIFICATION OF TUMOR STEM CELL SUBSETS 311
MULTIPLE DRUG RESISTANCE TRANSPORTERS AND CANCER STEM CELLS: TWO EXAMPLES 314
METHODS 322
ACKNOWLEDGMENTS 323
REFERENCES 323
Index 325

Produkt-Details

• Erscheint lt. Verlag: 20.4.2009
• Reihe/Serie: Cancer Drug Discovery and Development
• Reihe/Serie: Cancer Drug Discovery and Development
• Zusatzinfo: XVI, 346 p. 62 illus., 16 illus. in color.
• Verlagsort: Totowa
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Onkologie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• Schlagworte: angiogenesis • carcinoma • Chromosom • DNA • gene expression • genes • transcription
• ISBN-10: 1-60327-933-4 / 1603279334
• ISBN-13: 978-1-60327-933-8 / 9781603279338