Stem Cells and Cancer

1. Auflage 2009
ISBN: 978-1-60327-933-8
Verlag: Humana Press
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 346 Seiten

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.

Autoren/Hrsg.

Inhaltsverzeichnis

1;Preface;5
2;Contents;6
3;Contributors;9
4;Introduction to Cancer Stem Cells;14
4.1;The Cancer Stem Cell Hypothesis;15
4.1.1;THE CANCER STEM CELL MODEL OF CARCINOGENESIS;15
4.1.2;WHERE DO CANCER STEM CELLS COME FROM?;18
4.1.3;OPEN QUESTIONS: LIMITATIONS OF THE EXPERIMENTAL EVIDENCE;20
4.1.4;CLINICAL IMPLICATIONS: TARGETING CANCER STEM CELLS FOR THERAPY;22
4.1.5;CONCLUSIONS;24
4.1.6;REFERENCES;24
4.2;Tumor Stem Cells and Malignant Cells, One and the Same;27
4.2.1;INTRODUCTION;27
4.2.2;EARLY OBSERVATIONS;28
4.2.3;TUMOR CELL HETEROGENEITY;30
4.2.4;HEMATOPOIESIS AS A MODEL;31
4.2.5;METASTASIS;32
4.2.6;CARCINOGENESIS;34
4.2.7;CONCLUSIONS;35
4.2.8;REFERENCES;36
5;The Stem Cell Niche;39
5.1;Mesenchymal Stem Cells in Tumor Stroma;40
5.1.1;INTRODUCTION;40
5.1.2;MESENCHYMAL STEM CELLS;42
5.1.3;TUMOR STROMAGENESIS;42
5.1.4;TUMOR-ASSOCIATED FIBROBLASTS;42
5.1.5;THERAPEUTIC POTENTIAL OF MESENCHYMAL STEM CELLS;43
5.1.6;A THERAPEUTIC “DOUBLE-EDGED SWORD”;44
5.1.7;CONCLUSIONS;44
5.1.8;REFERENCES;45
6;Molecular Pathways and Gene Expression;48
6.1;Wnt Signaling in Cancer: From Embryogenesis to Stem Cell Self-Renewal;49
6.1.1;EMBRYOGENESIS AND ITS REQUIREMENTS;49
6.1.2;WNT SIGNAL TRANSDUCTION;50
6.1.3;CROSS-TALK BETWEEN WNT AND OTHER SIGNAL TRANSDUCTION PATHWAYS DURING EMBRYOGENESIS AND CANCER;53
6.1.4;WNT, NICHES, STEM CELLS, AND THEIR FATES;56
6.1.5;WNT IN STEM CELL HOMEOSTASIS AND REGENERATION;58
6.1.6;STEM CELLS AND CANCER;58
6.1.7;CONCLUSIONS: WNT: FROM EMBRYOGENESIS TO STEM CELL FATE AND CANCER;60
6.1.8;ACKNOWLEDGMENT;61
6.1.9;REFERENCES;61
6.2;PTEN in Hematopoietic and Intestinal Stem Cells and Cancer;68
6.2.1;INTRODUCTION;68
6.2.2;THE PTEN/PI3K/AKT SIGNALING PATHWAY;69
6.2.3;PTEN, HSCS, AND CANCER;71
6.2.4;PTEN, ISCS, AND CANCER;74
6.2.5;CONCLUDING REMARKS;77
6.2.6;REFERENCES;79
6.3;Transcription Factors in Cancer Stem Cells of the Hematopoietic Lineage;83
6.3.1;LEUKEMIC STEM CELLS;83
6.3.2;ROLE OF TRANSCRIPTION FACTORS IN NORMAL HEMATOPOIESIS;84
6.3.3;EFFECTS OF TRANSCRIPTION FACTORS IN NORMAL HEMATOPOIETIC STEM CELLS;85
6.3.4;ROLE OF TRANSCRIPTION FACTORS IN HUMAN LEUKEMIA;85
6.3.5;PU.1 DEREGULATION TRANSFORMS HEMATOPOIETIC STEM CELLS;86
6.3.6;CEBPA;87
6.3.7;OTHER TRANSCRIPTION FACTORS;89
6.3.8;REFERENCES;89
6.4;Stem Cell Chromatin Patterns and DNA Hypermethylation;92
6.4.1;THE EPIGENETIC TOOL BOX;92
6.4.2;EPIGENETIC CHANGES DURING NORMAL DEVELOPMENT;94
6.4.3;PROGENITOR CELLS AS TUMOR INITIATING CELLS;97
6.4.4;EPIGENETIC CHANGES DURING TUMOR INITIATION AND MALIGNANT PROGRESSION;98
6.4.5;POLYCOMB REPRESSIVE COMPLEXES: AN EPIGENETIC BRIDGE BETWEEN NORMAL AND MALIGNANT DEVELOPMENT?;100
6.4.6;REFERENCES;102
6.5;Plasticity Underlying Multipotent Tumor Stem Cells;105
6.5.1;THE STEM-CELL-LIKE NATURE OF CANCER;105
6.5.2;NODAL SIGNALING AND CELL FATE;107
6.5.3;NODAL AS A MEDIATOR AND BIOMARKER OF TUMOR PROGRESSION;110
6.5.4;REGULATION OF NODAL EXPRESSION: CONVERGENCE WITH NOTCH;112
6.5.5;EPIGENETIC REPROGRAMMING OF MULTIPOTENT TUMOR CELLS;113
6.5.6;REFERENCES;116
7;Cancer Stem Cells in Solid Tumors;119
7.1;Glioma Stem Cells in the Context of Oncogenesis;120
7.1.1;GLIOMAS CONTAIN HETEROGENEOUS TUMOR CELL POPULATIONS ACCORDING TO MORPHOLOGICAL CRITERIA;120
7.1.2;EVIDENCE FOR THE EXISTENCE OF GLIOMA STEM CELLS;122
7.1.3;GLIOMA STEM CELLS IN THE CONTEXT OF GLIOMA ONCOGENESIS;124
7.1.4;CLINICAL IMPLICATIONS OF GLIOMA STEM CELLS;127
7.1.5;CONCLUDING REMARKS;128
7.1.6;REFERENCES;128
7.2;Mouse Mammary Tumor Virus: Stem Cells and Mammary Cancer;132
7.2.1;INTRODUCTION;132
7.2.2;STEM/PROGENITOR CELL ACTIVITY IN MMTV-INDUCED TUMORS;133
7.2.3;STEM/PROGENITOR CELL HIERARCHY;135
7.2.4;SELECTIVE DNA SEGREGATION;137
7.2.5;ASYMMETRIC VERSUS SYMMETRIC CELL DIVISION IN CANCER;141
7.2.6;STEM/PROGENITOR CELLS ARE TARGETS FOR MMTV TRANSFORMATION;142
7.2.7;CONCLUSIONS;143
7.2.8;REFERENCES;143
7.3;Tumor Dormancy, Metastasis, and Cancer Stem Cells;146
7.3.1;INTRODUCTION;146
7.3.2;METASTASIS AND DORMANCY;147
7.3.3;THE CSC HYPOTHESIS;148
7.3.4;STEM CELLS, CANCER STEM CELLS, AND METASTATIC CELLS;150
7.3.5;THERAPEUTIC IMPLICATIONS;154
7.3.6;CONCLUDING REMARKS;154
7.3.7;ACKNOWLEDGMENTS;155
7.3.8;REFERENCES;155
7.4;Cancer Stem Cells: Gastrointestinal Cancers;159
7.4.1;INTRODUCTION;159
7.4.2;CANCER GENOMICS AND BIOLOGY IN GASTROINTESTINAL CANCERS;159
7.4.3;COLORECTAL CANCER;162
7.4.4;HEPATOCELLULAR CARCINOMA;164
7.4.5;ESOPHAGEAL AND STOMACH CANCER;164
7.4.6;PERSPECTIVE;165
7.4.7;REFERENCES;165
7.5;Cancer Stem Cells: Hepatocellular Carcinoma;168
7.5.1;INTRODUCTION;168
7.5.2;A STEM CELL ORIGIN OF LIVER TUMORS;169
7.5.3;LIVER CANCER STEM CELLS;171
7.5.4;CONCLUSION;175
7.5.5;REFERENCES;175
7.6;Cancer Stem Cells: Lung Cancer;179
7.6.1;ACKNOWLEDGMENTS;184
7.6.2;REFERENCES;184
7.7;Cancer Stem Cells: Pancreatic Cancer;187
7.7.1;PANCREATIC CANCER OVERVIEW;187
7.7.2;SIGNALING PATHWAYS CONTROLLING PANCREATIC CANCER DEVELOPMENT;188
7.7.3;ISOLATION OF PANCREATIC CANCER STEM CELLS;190
7.7.4;ALTERNATIVE CSC MARKERS?;191
7.7.5;IN VITRO CULTURE OF PANCREATIC CANCER STEM CELLS;192
7.7.6;PATHWAYS INVOLVED IN CONTROLLING PANCREATIC CSC FUNCTION;193
7.7.7;PANCREATIC CANCER STEM CELLS AND METASTASIS;194
7.7.8;PANCREATIC CANCER STEM CELLS AND RESISTANCE TO THERAPY;195
7.7.9;CANCER STEM CELL-BASED THERAPEUTICS;196
7.7.10;CONCLUSION;197
7.7.11;REFERENCES;197
7.8;Prostate Stem Cells and Cancer in Animals;200
7.8.1;INTRODUCTION;200
7.8.2;GROWTH ASSAYS FOR STEM CELLS FROM THE NORMAL PROSTATE;202
7.8.3;A PLACE CALLED HOME: STEM CELL LOCALIZATION AND NICHE;203
7.8.4;SEARCHING FOR THE INVISIBLE: ENRICHING FOR PROSTATIC PROGENITOR CELLS VIA STEM CELL MARKERS;205
7.8.5;MODELS OF DIFFERENTIATION;206
7.8.6;SEARCHING FOR PROSTATE CANCER STEM CELLS: MODEL SYSTEMS AND PROSPECTS;208
7.8.7;CONCLUSION;212
7.8.8;ACKNOWLEDGMENTS;213
7.8.9;REFERENCES;213
7.9;Prostate Cancer Stem/Progenitor Cells;218
7.9.1;INTRODUCTION;218
7.9.2;CELLULAR ORGANIZATION OF THE PROSTATIC GLAND;219
7.9.3;NORMAL HUMAN PROSTATE STEM/PROGENITOR CELLS;220
7.9.4;STEM-LIKE CELLS IN TUMORS AND PCa STEM/PROGENITOR CELLS;222
7.9.5;ACKNOWLEDGMENTS;228
7.9.6;BIBLIOGRAPHY;228
7.10;Adult Prostate Epithelium Renewal, Stem Cells and Cancer;232
7.10.1;INTRODUCTION;232
7.10.2;THE ADULT PROSTATE GLAND;233
7.10.3;DEVELOPMENT OF THE PROSTATE;233
7.10.4;PROSTATE EPITHELIUM HOMEOSTASIS;236
7.10.5;PROSTATE STEM CELL ASSAYS;238
7.10.6;ISOLATION OF PROSTATE STEM CELLS;240
7.10.7;PROSTATE STEM CELLS AND CANCER;241
7.10.8;CONCLUSIONS;242
7.10.9;REFERENCES;243
7.11;Stem Cells, Angiogenesis, and Neurogenesis in Tumors;248
7.11.1;INTRODUCTION;248
7.11.2;SIMILARITIES BETWEEN TUMOR ANGIOGENESIS AND INNERVATION;249
7.11.3;NEUROTROPHIC FACTORS THAT PROMOTE ANGIOGENESIS;249
7.11.4;ANGIOGENIC FACTORS THAT PROMOTE NEURONAL OUTGROWTH;250
7.11.5;BONE-MARROW-DERIVED STEM CELLS IN TUMORS;250
7.11.6;CONCLUSIONS;251
7.11.7;REFERENCES;251
8;Targeting Cancer Stem Cells with Therapy;254
8.1;Implications of Cancer Stem Cells for Cancer Therapy;255
8.1.1;INTRODUCTION;255
8.1.2;CSC AND PRECANCEROUS LESIONS: CLINICAL IMPLICATIONS;256
8.1.3;CSC AND MESENCHYMAL STEM CELLS;257
8.1.4;RADIATION AND DRUG RESISTANCE OF CSC;257
8.1.5;CSC AND CANCER RELAPSE;258
8.1.6;CSC AND CANCER METASTASIS;258
8.1.7;CSC AND PROGNOSIS;258
8.1.8;THERAPEUTICS TARGETING CSC;258
8.1.9;SURFACE MOLECULE TARGETING THERAPY;259
8.1.10;ONCOPROTEIN TARGETING THERAPY;259
8.1.11;STEM CELL REGULATION PATHWAY TARGETING;260
8.1.12;DRUG AND RADIATION RESISTANCE INHIBITORS;260
8.1.13;MESENCHYMAL STEM CELLS AND ANTI-NICHE CSC THERAPY;260
8.1.14;CONCLUSIONS;261
8.1.15;REFERENCES;261
8.2;Targeting Leukemic Stem Cells;263
8.2.1;BACKGROUND;263
8.2.2;HEMATOPOIETIC AND LEUKEMIC STEM CELLS: COMMONALITIES AND DIFFERENCES;264
8.2.3;LEUKEMIC STEM CELL TYPES;264
8.2.4;TARGETS IN LSCS;266
8.2.5;CONCLUSIONS AND FUTURE PERSPECTIVES;271
8.2.6;ACKNOWLEDGMENTS;272
8.2.7;REFERENCES;272
8.3;Targeting Brain Cancer Stem Cells in the Clinic;274
8.3.1;IDENTIFICATION AND ISOLATION OF BRAIN CANCER STEM CELLS;274
8.3.2;CANCER STEM CELLS IN THERAPEUTIC RESISTANCE;276
8.3.3;CANCER STEM CELLS IN PROGNOSIS;277
8.3.4;DIFFERENTIATION THERAPY;278
8.3.5;TARGETING SIGNAL TRANSDUCTION PATHWAYS OF CANCER STEM CELLS;278
8.3.6;TARGETING CANCER STEM CELLS USING ACTIVE IMMUNOTHERAPY;279
8.3.7;TARGETING CANCER STEM CELLS WITH PASSIVE IMMUNOTHERAPY;281
8.3.8;SUMMARY;282
8.3.9;REFERENCES;282
8.4;Critical Roles of Tumorigenic and Migrating Cancer Stem/ Progenitor Cells in Cancer Progression and their Therapeutic Implications;286
8.4.1;INTRODUCTION;286
8.4.2;FUNCTIONS OF TUMORIGENIC AND MIGRATING CANCER STEM/ PROGENITOR CELLS IN CANCER PROGRESSION AND METASTASES;288
8.4.3;NEW CONCEPT ON HETEROGENEITY OF CANCERS DERIVED FROM DISTINCT TUMORIGENIC AND MIGRATING CANCER STEM/ PROGENITOR CELLS;293
8.4.4;NOVEL THERAPIES AGAINST AGGRESSIVE AND RECURRENT CANCERS;295
8.4.5;CONCLUSIONS AND FUTURE RESEARCH;298
8.4.6;ACKNOWLEDGMENTS;298
8.4.7;REFERENCES;299
8.5;Therapeutic Index and the Cancer Stem Cell Paradigm;308
8.5.1;INTRODUCTION;308
8.5.2;TUMOR HETEROGENEITY AND THE IDENTIFICATION OF TUMOR STEM CELL SUBSETS;311
8.5.3;MULTIPLE DRUG RESISTANCE TRANSPORTERS AND CANCER STEM CELLS: TWO EXAMPLES;314
8.5.4;METHODS;322
8.5.5;ACKNOWLEDGMENTS;323
8.5.6;REFERENCES;323
9;Index;325