Growth Factors and their Receptors in Cell Differentiation, Cancer and Cancer Therapy

By: Gajanan Sherbet

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Hardcover | 14 July 2011 | Edition Number 1

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Hardcover
368 Pages

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22.9 x 15.2 x 2.06

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Recent years have seen a considerable emphasis on growth factors and the elucidation of their mode of function, which has led to the recognition that growth factors, their receptors as well as downstream elements of signalling associated with their function might be potential targets in therapeutic management of human diseases. Humanised monoclonal antibodies raised against growth factor receptors have proved to be valuable for targeted cancer treatment and in patient management.

This book reviews the latest developments providing insights into the signalling processes involved in morphogenesis and pathogenesis with emphasis on using the elements of the signalling cascades as targets for therapeutic deployment.

Provides aÿfundamental understanding of the basic functions of growth factors and their receptors, describing how they are linked in biological processes
Aids the development of therapeutic treatments for cancer
Focuses on the interrelationships and convergence of growth factors and their receptors in development and pathogenesis and encourages greater cooperation and integration in the areas of developmental, cancer and cancer therapeutic research

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Non-Fiction Medicine Pre-Clinical Medicine & Basic Sciences Human Reproduction, Growth & Development Reproductive Medicine Embryology Science Biology, Life Sciences Biochemistry Nursing & Ancillary Services Biomedical Engineering Life Sciences in General

Genetics excluding Medical Developmental Biology Clinical & Internal Medicine Diseases & Disorders Oncology

Preface	p. xi
Abbreviations	p. xiii
Introduction	p. xvii
Convergence of Growth-Factor Signalling Pathways in Developmental Systems and Pathogenesis	p. 1
Growth Factor Families	p. 3
The Membrane-Receptor Binding Family of Growth Factors	p. 3
Cystine-Knot Group of Growth Factors	p. 3
The Intracellular-Receptor Binding Family of Ligands	p. 5
Growth Factors in Differentiation and Morphogenesis	p. 7
TGF-ß Family Growth Factors in Differentiation and Morphogenesis	p. 8
TGF-ß in Tumour Growth, Invasion and Metastases	p. 9
The TGF-ß Signalling Cascade	p. 10
The TGF-ß Receptor Group	p. 11
Receptor Types I and II in Signalling by TGF-ß Ligands	p. 11
Receptor Type III Endoglin-Mediated TGF-ß Signalling	p. 11
Receptor Type III Betaglycan in TGF-ß Signalling	p. 12
The Canonical Smad Pathway	p. 12
The Effects of TGF-ß on Cell Proliferation and Apoptosis	p. 13
Cell Proliferation, Invasion and Metastasis Mediated by Type III Receptors	p. 15
Endoglin as a Chemotherapeutic Target	p. 17
Therapeutic Potential of Betaglycan	p. 17
TGF-ß and Organ-Specific Metastatic Spread	p. 18
Non-Smad (Non-Canonical) Signalling	p. 20
Non-Canonical TGF-ß Signalling in Cancer Invasion and Angiogenesis	p. 22
MicroRNAs, EMT and TGF-ß Function	p. 23
TGF-ß Operates in Other Signalling Systems of Cell Adhesion and Motility	p. 27
Interaction between Smad and Non-Smad Signalling	p. 28
Signalling Links between BMP, Oestrogen and ER	p. 29
Functional Synergy and Regulation between Smad and MAPK Pathways	p. 30
Nodal Signalling in Development, Differentiation and Pattern Formation	p. 31
Regulation of Nodal Signalling	p. 31
Differential Activation of Contributory Pathways	p. 31
Selective and Differential Activation of Transcription Factors	p. 32
Nodal, miRNA and EMT	p. 34
Requirement of Cofactors in Nodal Regulation	p. 34
Functional Stability of Nodal	p. 35
Bone Morphogenetic Proteins	p. 36
Heterogeneity of BMP Signalling Cascade and Phenolypic Effects	p. 38
Growth and Differentiation Factors	p. 45
GDFs in Development and Differentiation	p. 45
Co-ordination of GDF Signalling with Other TGF-ß Family Members	p. 46
Synergistic Signalling of GDFs with BMPs	p. 46
GDF and Nodal Signalling in Embryonic Development	p. 50
Collaborative Function of GDFs and Hormones	p. 51
GDF Expression in Cancer	p. 51
Activin and Inhibin Signalling	p. 52
Signalling Antagonism between Activin and Inhibin	p. 53
Vascular Endothelial Growth Factor	p. 55
VEGF Signalling	p. 55
Angiogenic Properties of VEGF Proximal and Distal Splice Variants	p. 56
Synergy of VEGF with Other Angiogenic Signalling Systems	p. 57
Notch Signalling in Angiogenesis	p. 58
Sphingosine 1-Phosphate (S1P) Cross-Talk in VEGF Signalling	p. 58
The Interaction of ADAM Proteins with VEGF Signalling	p. 59
Genetic Polymorphism in VEGF in Disease Slates	p. 59
Is the Production of SNPs and VEGF Linked?	p. 60
Functional Synergy of SNPs of Angiogenic Agents	p. 60
Neovascularisation and Tumour Progression	p. 61
Targeting VEGF and VEGFR in Cancer Treatment	p. 62
Hepatocyte Growth Factor	p. 65
Molecular Structure of HGF	p. 65
HGF/MET Signalling	p. 65
MET as a Therapeutic Target	p. 69
The Platelet-Derived Growth Factor Family	p. 71
PDGF in Cell Transformation and Cancer	p. 72
Putative Collaborative Participation of PDGF in Angiogenic Signalling	p. 72
PDGF and Epithelial-Mesenchymal Transition	p. 72
PDGF Signalling in Cell Proliferation and Migration	p. 74
Co-operation with GPCR Pathway in Mitogenic Function	p. 75
Signalling Specificity	p. 75
PDGF Activates ets-1 Transcription Factor	p. 75
Early Growth Response (egr) Zinc Finger Transcription Factors	p. 76
MCP-1 in PDGF Effect	p. 77
Relationship of PDGF Expression to Cancer Invasion and Progression	p. 78
Genetic Changes in PDGFs and PDGFRs	p. 79
Nerve Growth Factors	p. 81
NT Signalling	p. 81
Genetic Alterations in NT Receptors	p. 82
Expression of NTs and Their Receptors in Cancer	p. 84
Insulin-Like Growth Factors	p. 87
Insulin-Like Growth Factors and Their Receptors	p. 87
Insulin-Like Growth Factor Receptors	p. 87
Insulin Receptor Substrate Proteins	p. 87
IGF Signalling Pathways	p. 88
IGF Signalling Interacts with Other Signalling Systems	p. 90
The Interaction of Insulin and Growth Hormone with IGF Signalling	p. 90
IGF Cross-Talk with Cell Proliferation and Migration Signalling	p. 92
IGF Induces VEGF Expression and Vascularisation	p. 93
Integration of Notch Signalling by IGF	p. 95
IGF and the Morphogenetic Function of Wnt Proteins	p. 96
Leptin Synergy with IGF Function	p. 97
IGF Expression in Cancers	p. 100
Modulation of Migration by IGFs and Their Receptors	p. 102
Connective Tissue Growth Factor	p. 105
CTGF in Wound Healing and Fibrosis	p. 105
CTGF Expression Correlates with Cancer Progression and Prognosis	p. 106
Is CTGF Involved in Osteotropic Metastasis?	p. 107
Pro-angiogenic Effect of CTGF	p. 108
Regulation of CTGF by TGF-ß	p. 109
Thrombospondins	p. 111
TSPs in Cancer	p. 112
Cytokines	p. 115
Tumour Necrosis Factors	p. 115
TNF, Cell Proliferation and Apoptosis	p. 117
TNF, Angiogenesis, Cancer Invasion and Metastasis	p. 117
Targeting TNF- Function through MicroRNAs	p. 119
Interleukins	p. 119
Interleukins Induce Cell Motility	p. 120
Angiogenic Effects of Interleukins	p. 121
Interferons	p. 122
IFNs in Cancer Progression	p. 123
Cytokines and Myeloid Differentiation	p. 124
Granulocyte-Macrophage (GM-CSF), Granulocyte (G-CSF) and Macrophage (M-CSF) Colony-Stimulating Factors	p. 125
Cytokines in Cancer Therapy	p. 126
Chemokines	p. 128
IFN-Induced Chemokines in Cancer Invasion	p. 129
Monocyte Chemoattractant Protein (MCP)	p. 131
MCP-1 Expression in Cancers	p. 131
Growth Factor and Hedgehog Signalling Pathways Meet in Developmental Systems	p. 133
The Hedgehog (Hh) Proteins	p. 133
The Hh Signalling Cascade	p. 134
Hh Homologues and Their Role in Morphogenesis	p. 136
Co-operative Signalling by Hh and Growth Factors	p. 138
TGF-ß Family Ligands and Hh Signalling	p. 138
FGF and Hh Signalling	p. 139
Epidermal Growth Factors and Their Signalling Systems	p. 141
Growth Factor Signal Transduction	p. 141
Epidermal Growth Factor (EGF) Family Ligands and Receptors	p. 141
EGF Signalling Pathways	p. 144
EGF Signalling through CD44	p. 147
GPCRs in Growth Factor Signalling	p. 149
The Wnt/ß-catenin Pathway in Growth Factor Signalling	p. 150
Hedgehog Signalling in EGFR Function	p. 151
Negative Regulation of EGFR Signalling	p. 152
Preferential Receptor Activation and Transactivation	p. 153
Metastasis Suppressor Genes and Growth Factor Signalling	p. 154
Nm23 Interaction with Growth Factor Function	p. 156
Growth Factor Receptor Expression in Cancer	p. 160
EGF Family Receptors in Cancer Therapy	p. 161
Treatment of Triple-negative Breast Cancer	p. 165
The Epidermal Growth Factor (EGF) Family	p. 173
Structure, Function and Expression of Epidermal Growth Factor (EGF) and EGF Receptor	p. 173
Single Nucleotide Polymorphism of EGF and Its Significance	p. 174
Function of Transforming Growth factor (TGF)-	p. 176
Neuregulins (Heregulins)	p. 178
Amphiregulin (AREG)	p. 183
Differential Signalling by AREG	p. 183
AREG in Cell Proliferation	p. 184
AREG in Invasion and Metastasis	p. 185
AREG Expression in Human Neoplasms	p. 191
Epiregulin (EREG)	p. 192
EREG Expression in Cancers	p. 193
ß-Cellulin (BTC)	p. 194
BTC Expression in Cancers	p. 195
Heparin-Binding Epidermal Growth Factor-Like Growth Factor	p. 195
HB-EGF Induces Angiogenesis	p. 195
Influence of HB-EGF on Cell Motility and Invasion	p. 196
HB-EGF in Cancer Progression	p. 197
The Fibroblast Growth Factor Family	p. 199
FGFs in the Development of the Central Nervous System and Neuronal Differentiation	p. 201
FGF2 (Basic FGF)	p. 204
FGF2-Mediated Promotion of Intercellular Adhesion	p. 205
FGF2 and Promotion of Neurite Extension	p. 205
FGF2 and Osteogenesis	p. 207
FGFs 1 and 2 Regulate Cell Proliferation	p. 208
FGFs 1 and 2 and the Induction of Angiogenesis	p. 208
Intracellular Receptor Binding Growth Factors	p. 211
The Androgens and Androgen Receptors in Development, Differentiation and Neoplasia	p. 213
Androgen Receptor and Androgen-Responsive Elements	p. 213
AR-Activated Signalling Pathways	p. 214
AR Expression in Cancer Progression	p. 216
Functional Integrity of AR and AR-Mediated Signalling	p. 217
Interaction of Androgen and Growth Factor Signalling	p. 217
Vitamin D₃ in Cell Proliferation, Apoptosis and Differentiation	p. 219
The VD3 Receptor, VDRs and VDR Response Elements	p. 219
VDR Signalling in Cell Proliferation, Apoptosis and Differentiation	p. 220
Modulation of Cell Adhesion and Motility	p. 221
Collaborative Function of VDR and RA Receptors	p. 223
Retinoids in Development and Pattern Formation	p. 225
Retinoic Acid Receptors	p. 225
RAR-Mediated Biological Effects	p. 225
Oestrogens and Progesterone in Normal Physiology and Neoplasia	p. 229
Receptor Mediation of Oestrogen and Progesterone Function	p. 229
ER/PR in Cell Adhesion, Proliferation and Cross-talk with Growth Factor Signalling	p. 230
ER Signalling and Cell Motility	p. 230
ER and Cell Proliferation	p. 231
ER/PR Cross-talk with Tumour Suppressor and Promoter Signalling	p. 232
The Trefoil Protein TFF1	p. 234
TFF1, Cell Proliferation and Invasion	p. 234
TFFs in Progression and Prognosis	p. 235
Glucocorticoid Signalling in Normal and Aberrant Physiology	p. 237
Glucocorticoid Receptors in Signalling	p. 237
Effects of Glucocorticoids on Cell Function	p. 239
Regulation of Cell Proliferation	p. 239
Modulation of Extracellular Matrix Enzyme Systems	p. 240
Glucocorticoids and Cancer Progression	p. 241
Epilogue	p. 243
References	p. 249
Table of Contents provided by Ingram. All Rights Reserved.

Growth Factors and their Receptors in Cell Differentiation, Cancer and Cancer Therapy

At a Glance

Hardcover

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Defective items

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