Chemokine Receptors in Cancer

1. Auflage 2009
ISBN: 978-1-60327-267-4
Verlag: Humana Press
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 172 Seiten

Chemokines are a superfamily of low molecular weight cytokines that were initially described based on their ability to induce the directed migration of leukocytes to sites of inflammation or injury. In humans, there are approximately 45 chemokines that bind to 19 G-protein-coupled receptors. In addition to mediating cellular migration, chemokines have now been shown to affect many cellular functions including survival, adhesion, invasion, proliferation, and to regulate circulating chemokine levels. Although chemokine receptors were first described on leukocytes, it is now appreciated that chemokine receptors are also expressed by many other cells including endothelial and epithelial cells. Since the first description of chemokine receptors on malignant cells in 2001, an extensive literature has developed describing the expression and function of chemokine receptors in many malignancies. These studies support the initial hypothesis that malignant cells use chemokine receptors to migrate to distant sites of ligand expression and that expression of certain receptors is associated with a poor prognosis. It has also become apparent that malignancies of different tissues may use a diverse profile of chemokine receptors and that the same receptor may mediate metastasis to different sites in tumors of different histological origins. Receptor function may also maintain survival and expansion of the primary tumor.

Autoren/Hrsg.

Inhaltsverzeichnis

1;Preface;5
2;Contents;7
3;Contributors;8
4;Chemokines and Chemokine Receptors in Cancer Progression;10
4.1;Introduction;33
4.2;Tumourigenesis, Invasion and Metastasis;11
4.2.1;Tumour Metastasis and the Hypothesis of ‘‘Seed’’ and ‘‘Soil’’;12
4.2.2;Molecular Mechanisms of Cancer Metastatic Progression;12
4.3;Chemokines and Chemokine Receptors in Cancer Progression;14
4.3.1;Introduction;14
4.3.2;Chemokines and the Tumour Immune Response;14
4.3.3;Chemokines in Tumor Development, Growth and Angiogenesis;17
4.3.4;Chemokines in Tumor Invasion and Metastasis;18
4.4;Cross-Talk Between Chemokines and Growth Factors in Cancer Progression;20
4.4.1;IGF System in Breast Cancer Progression;21
4.4.2;Evidence for Cross-Talk Between CXCR4 and IGF-1R Signal Transduction in Breast Cancer Metastasis;23
4.5;Functional Relationship between Chemokine Receptors and the Metastatic Phenotype of Breast Cancer Cells;27
4.5.1;Expression of Chemokine Receptors and Cancer Metastasis;27
4.5.2;Functional Activation of Chemokine Receptors and Cancer Metastasis;28
4.5.3;Molecular Mechanisms of the Functional On-Switch of the Chemokine Receptors in Metastatic Cancer Cells;29
4.6;Conclusion and Perspective;32
4.7;References;33
5;CXCR4 and Cancer;40
5.1;The Chemokine Receptor CXCR4 and Cancer;40
5.2;Concept of Cancer Stem Cells;42
5.3;The Role of CXCR4-SDF-1 Axis Involved in Mobilization, Trafficking, and Homing of Cancer Stem Cells;43
5.4;CXCR4 Receptor Expression, Regulation, and Pathway;43
5.5;Conclusion and Future Directions;46
5.6;References;47
6;HIF-1 Regulation of Chemokine Receptor Expression;55
6.1;Introduction;55
6.2;Hypoxia-Inducible Factor-1;56
6.3;The Chemokine-Chemokine Receptor System;57
6.4;HIF-1 Dependent and Independent Pathways for VEGF-Induced Angiogenesis;57
6.5;Hypoxia and Upregulation of Chemokine Receptors CXCR1 and CXCR2 Expression;58
6.6;Hypoxia and Upregulation of Chemokine Receptor CXCR7 Expression;59
6.7;Hypoxia and Upregulation of Chemokine Receptor CXCR4 Expression in Glioma;60
6.8;Potential Therapeutic Targeting of Chemokine Receptors to Inhibit Tumor Growth;62
6.9;References;64
7;Chemokine Receptors Involved in Colon Cancer Progression, and Lymph Node Metastasis;70
7.1;Chemokines and Their Receptors in Cancer;71
7.2;Genetic Changes in Colon Cancer Progression and Stromal Reactions;71
7.3;Tumor-Stromal Interaction in Colon Cancer Invasion: A Mouse Model;72
7.4;From ‘‘Molecular Target’’ Therapy to ‘‘Cellular Target’’ Therapy;73
7.5;CCR1 Antagonists;74
7.6;Chemokine Receptor CXCR3 and Lymph Node Metastasis;75
7.7;Expression of CXCR3 in Colon Cancer Cell Lines;75
7.8;Enhanced Metastasis of DLD-1-CXCR3 Cells to Draining Lymph Nodes;76
7.9;CXCR3 Expression in Clinical Colon Cancer Samples;79
7.10;Cancer Metastasis and Chemokine-Chemokine Receptor System;79
7.11;Clinical Significance of LN Metastasis;81
7.12;Roles of Chemokine-Chemokine Receptor System in Other Aspects of Cancer Biology;82
7.13;References;83
8;The CXCR3/CXCL3 Axis in Cancer;86
8.1;Properties of CXCR3;87
8.2;CXCR3 Expression in Malignancy;88
8.3;Melanoma;88
8.4;Breast Cancer;89
8.5;Colon Carcinoma;91
8.6;Prostate Cancer;91
8.7;Other Solid Tumors;92
8.8;Exceptions to the Rule;92
8.9;What Are the Roles of CXCR3 Ligands in Tumor Behavior?;93
8.10;Summary;95
8.11;References;96
9;Roles for CCR7 in Cancer Biology;99
9.1;Introduction;99
9.2;Expression of CCR7 and Its Ligands;100
9.3;CCR7 in Cancer Biology;101
9.4;CCR7 Expression by Human Cancers and Its Correlation with Nodal Metastases and Poor Prognosis;101
9.5;Mechanisms that Promote CCR7 Upregulation in Human Cancers;103
9.6;Effects of CCR7 Expression on Cancer Cell Chemotaxis, Invasion, and Tumor Formation;104
9.7;Mechanisms of Tumor Cell Homing to Lymphatics;107
9.8;Effects of CCR7 Expression by CD8 T Cells and Mature DCs in Cancer Immunotherapy;107
9.9;Summary;109
9.10;References;109
10;The CCL5/CCR5 Axis in Cancer;115
10.1;Introduction;116
10.2;The CCL5/CCR5 Axis in Hematological Malignancies: Multiple Myeloma;117
10.3;The CCL5/CCR5 Axis in Solid Tumors;119
10.3.1;Breast Cancer;119
10.3.2;Melanoma;124
10.3.3;Gastric Cancer;126
10.3.4;Ovarian Cancer;127
10.4;Conclusions;128
10.5;References;130
11;CXC Chemokines in Cancer Angiogenesis;137
11.1;Introduction;137
11.2;Angiogenic CXC Chemokines;138
11.2.1;CXCR2: The Key Receptor for Angiogenic CXC Chemokines;138
11.2.2;Involvement of Other Receptors in Chemokine-Mediated Angiogenesis;139
11.2.3;Interaction of Angiogenic CXC Chemokine Ligands with Matrix Metalloproteinases;140
11.2.4;Angiogenic CXC Chemokines in Malignancy;141
11.3;Angiostatic CXC Chemokines;143
11.3.1;CXCR3: The Main Receptor for Angiostatic CXC Chemokines;144
11.3.2;CXCR3-Independent Angiostatic Activity of CXCL4;145
11.3.3;CXCR7: A Novel CXC Chemokine Receptor;146
11.3.4;Angiostatic CXC Chemokines Attenuate Angiogenesis Associated with Tumorigenesis;147
11.3.5;Immunoangiostasis: The Role of CXCR3/CXCR3 Ligand Biological Axis in Mediating Th1 Cell-Mediated Immunity and Angiostasis;148
11.4;Conclusion;149
11.5;References;149
12;The Roles of Chemokines and Chemokine Receptors in Prostate Cancer;158
12.1;Introduction;158
12.2;Role of Chemokines and Their Receptors in Prostate Cancer Angiogenesis and Tumor Growth;159
12.3;Role of Chemokines and Their Receptors in Prostate Cancer Invasion and Metastasis;162
12.4;Role of Decoy Receptors in Prostate Cancer;164
12.5;Future Perspective;167
12.6;Conclusion;168
12.7;References;169
13;Index;176