Chemokine Receptors in Cancer (eBook)

Preface 5
Contents 7
Contributors 8
Chemokines and Chemokine Receptors in Cancer Progression 10
Introduction 33
Tumourigenesis, Invasion and Metastasis 11
Tumour Metastasis and the Hypothesis of ‘‘Seed’’ and ‘‘Soil’’ 12
Molecular Mechanisms of Cancer Metastatic Progression 12
Chemokines and Chemokine Receptors in Cancer Progression 14
Introduction 14
Chemokines and the Tumour Immune Response 14
Chemokines in Tumor Development, Growth and Angiogenesis 17
Chemokines in Tumor Invasion and Metastasis 18
Cross-Talk Between Chemokines and Growth Factors in Cancer Progression 20
IGF System in Breast Cancer Progression 21
Evidence for Cross-Talk Between CXCR4 and IGF-1R Signal Transduction in Breast Cancer Metastasis 23
Functional Relationship between Chemokine Receptors and the Metastatic Phenotype of Breast Cancer Cells 27
Expression of Chemokine Receptors and Cancer Metastasis 27
Functional Activation of Chemokine Receptors and Cancer Metastasis 28
Molecular Mechanisms of the Functional On-Switch of the Chemokine Receptors in Metastatic Cancer Cells 29
Conclusion and Perspective 32
References 33
CXCR4 and Cancer 40
The Chemokine Receptor CXCR4 and Cancer 40
Concept of Cancer Stem Cells 42
The Role of CXCR4-SDF-1 Axis Involved in Mobilization, Trafficking, and Homing of Cancer Stem Cells 43
CXCR4 Receptor Expression, Regulation, and Pathway 43
Conclusion and Future Directions 46
References 47
HIF-1 Regulation of Chemokine Receptor Expression 55
Introduction 55
Hypoxia-Inducible Factor-1 56
The Chemokine-Chemokine Receptor System 57
HIF-1 Dependent and Independent Pathways for VEGF-Induced Angiogenesis 57
Hypoxia and Upregulation of Chemokine Receptors CXCR1 and CXCR2 Expression 58
Hypoxia and Upregulation of Chemokine Receptor CXCR7 Expression 59
Hypoxia and Upregulation of Chemokine Receptor CXCR4 Expression in Glioma 60
Potential Therapeutic Targeting of Chemokine Receptors to Inhibit Tumor Growth 62
References 64
Chemokine Receptors Involved in Colon Cancer Progression, and Lymph Node Metastasis 70
Chemokines and Their Receptors in Cancer 71
Genetic Changes in Colon Cancer Progression and Stromal Reactions 71
Tumor-Stromal Interaction in Colon Cancer Invasion: A Mouse Model 72
From ‘‘Molecular Target’’ Therapy to ‘‘Cellular Target’’ Therapy 73
CCR1 Antagonists 74
Chemokine Receptor CXCR3 and Lymph Node Metastasis 75
Expression of CXCR3 in Colon Cancer Cell Lines 75
Enhanced Metastasis of DLD-1-CXCR3 Cells to Draining Lymph Nodes 76
CXCR3 Expression in Clinical Colon Cancer Samples 79
Cancer Metastasis and Chemokine-Chemokine Receptor System 79
Clinical Significance of LN Metastasis 81
Roles of Chemokine-Chemokine Receptor System in Other Aspects of Cancer Biology 82
References 83
The CXCR3/CXCL3 Axis in Cancer 86
Properties of CXCR3 87
CXCR3 Expression in Malignancy 88
Melanoma 88
Breast Cancer 89
Colon Carcinoma 91
Prostate Cancer 91
Other Solid Tumors 92
Exceptions to the Rule 92
What Are the Roles of CXCR3 Ligands in Tumor Behavior? 93
Summary 95
References 96
Roles for CCR7 in Cancer Biology 99
Introduction 99
Expression of CCR7 and Its Ligands 100
CCR7 in Cancer Biology 101
CCR7 Expression by Human Cancers and Its Correlation with Nodal Metastases and Poor Prognosis 101
Mechanisms that Promote CCR7 Upregulation in Human Cancers 103
Effects of CCR7 Expression on Cancer Cell Chemotaxis, Invasion, and Tumor Formation 104
Mechanisms of Tumor Cell Homing to Lymphatics 107
Effects of CCR7 Expression by CD8 T Cells and Mature DCs in Cancer Immunotherapy 107
Summary 109
References 109
The CCL5/CCR5 Axis in Cancer 115
Introduction 116
The CCL5/CCR5 Axis in Hematological Malignancies: Multiple Myeloma 117
The CCL5/CCR5 Axis in Solid Tumors 119
Breast Cancer 119
Melanoma 124
Gastric Cancer 126
Ovarian Cancer 127
Conclusions 128
References 130
CXC Chemokines in Cancer Angiogenesis 137
Introduction 137
Angiogenic CXC Chemokines 138
CXCR2: The Key Receptor for Angiogenic CXC Chemokines 138
Involvement of Other Receptors in Chemokine-Mediated Angiogenesis 139
Interaction of Angiogenic CXC Chemokine Ligands with Matrix Metalloproteinases 140
Angiogenic CXC Chemokines in Malignancy 141
Angiostatic CXC Chemokines 143
CXCR3: The Main Receptor for Angiostatic CXC Chemokines 144
CXCR3-Independent Angiostatic Activity of CXCL4 145
CXCR7: A Novel CXC Chemokine Receptor 146
Angiostatic CXC Chemokines Attenuate Angiogenesis Associated with Tumorigenesis 147
Immunoangiostasis: The Role of CXCR3/CXCR3 Ligand Biological Axis in Mediating Th1 Cell-Mediated Immunity and Angiostasis 148
Conclusion 149
References 149
The Roles of Chemokines and Chemokine Receptors in Prostate Cancer 158
Introduction 158
Role of Chemokines and Their Receptors in Prostate Cancer Angiogenesis and Tumor Growth 159
Role of Chemokines and Their Receptors in Prostate Cancer Invasion and Metastasis 162
Role of Decoy Receptors in Prostate Cancer 164
Future Perspective 167
Conclusion 168
References 169
Index 176