Cell Fusion in Health and Disease (eBook)

Preface 6
Contents 9
Contributors 10
1 Introduction 12
2 Horizontal Gene Transfers with or without Cell Fusions in All Categories of the Living Matter 15
2.1 Acquisition and Horizontal Transfer of Vibrio cholerae Virulence Gene 15
2.1.1 Hamburg 1892 15
2.1.2 The Vibrio and the Disease 16
2.1.3 The Phage and Its Genome 19
2.1.4 The Hiding Place of the Original Cholera Virulence Genes 21
2.2 Mimivirus and Its Companions 23
2.2.1 Viruses and Toxins of Blooming Dinoflagellates 23
2.2.2 Genes of the Mimivirus Shared with Its Phage and with Its Host Amoeba 26
2.3 Interviral (Virus-to-Virus) Gene Transfers 29
2.3.1 Marek's Disease Herpesvirus 29
2.3.2 Reticuloendotheliosis Virus Genomic Sequences in the Marek's Virus and in the Fowlpox Virus Genomes 29
2.3.3 Herpesviruses Activate Latent Retroviruses 32
2.3.4 Avian Herpesviruses Descend from Theropod Dinosaurs? 32
2.4 Horizontal Gene Transfers in Archaea and Prokaryota 36
2.4.1 The Darwinian Threshold (Woese) 36
2.4.2 The Ancient Origin of ''Virulence Genes'' 39
2.4.3 A Selected Example of Speciation 41
2.5 The Insertion of Adaptive Immunity Genes 44
2.5.1 Retrotransposons 44
2.5.2 An Ancient Herpesvirus 47
2.6 Horizontal Gene Gains in Eukaryota 49
2.6.1 Viral Genes 49
2.6.1.1 Bornavirus in Human Brain Cells 49
2.6.1.2 Human Herpesvirus-6 in Human Telomers 51
2.6.2 Horizontal Gene Transfers in Eukaryota 52
2.7 Epithelial-to-Mesenchymal Transition of Human Cancer Cells 58
2.7.1 Bacteria Inducing Inflammatory Cancers 58
2.7.1.1 Helicobacter Pylori: Cancers of the Soil and Seed 58
2.7.1.2 Bacteroides Fragilis: Inflammatory Carcinogenesis with or Without It 59
2.7.2 The Epithelial-to-Mesenchymal Transformation 64
2.8 Horizontal Transfer of Proto-Oncogenes 66
2.9 Horizontal Gene Transfers for the Treatment and Cure of Cancer 67
2.10 Consequences 68
2.11 Summary 69
References 70
3 Class III Viral Membrane Fusion Proteins 100
3.1 Introduction 100
3.1.1 Definition of Class III Fusion Proteins 100
3.1.2 Viruses Encoding Class III Fusion Proteins 101
3.1.3 The Multiple Roles of Class III Fusion Proteins 101
3.2 Structural Features of Class III Viral Fusion Proteins 102
3.2.1 Global Structural Organization of Class III Fusion Proteins 102
3.2.2 Domain Organization of Class III Fusion Proteins 103
3.3 Functionally Important Regions of Class III Fusion Proteins 104
3.3.1 Fusion Loops 104
3.3.2 Membrane-Proximal (Stem) Regions and C-Terminal Domain (CTD) 105
3.4 Molecular Basis of the Class III Type Proteins Fusion Mechanism 106
3.4.1 Activation Triggers for Class III Viral Fusogens 106
3.4.2 Structural Rearrangements of Class III Fusion Proteins 106
References 107
4 Human Trophoblast in Trisomy 21: A Model for Cell--Cell Fusion Dynamic Investigation 111
4.1 Human Placenta and Trophoblast Differentiation 111
4.2 Membranes Proteins Involved in Human Trophoblast Fusion and Differentiation 112
4.2.1 Syncytin-1 114
4.2.2 Syncytin-2 114
4.2.3 Syncytin-1 and Syncytin-2 Expression During In Vitro Trophoblast Differentiation 115
4.3 Abnormal Trophoblast Fusion and Differentiation in Trisomy 21 115
4.4 CellCell Fusion: A Dynamic Process 116
4.5 In Vitro Reversibility of Abnormal Trophoblast Fusion and Differentiation in T21 116
References 118
5 Cell Fusion and Hyperactive Osteoclastogenesis in Multiple Myeloma 121
5.1 Introduction 121
5.2 Cell Fusion in Multiple Myeloma 122
5.2.1 Ploidy Abnormalities 123
5.2.2 Centrosome Amplification 123
5.2.3 Myeloma Stem Cells 124
5.2.4 Macrophage Fusion and Metastatic Potential of Malignant Plasma Cells 125
5.2.5 Upregulated Osteoclastogenesis 126
5.3 The Origin and Role of the Osteoclasts in MM 126
5.3.1 Enhanced Marrow Levels of Osteoclastogenic Factors 126
5.3.2 Osteoclast-Like Myeloma Polykaryons 127
5.3.3 Osteoclast-Myeloma Hybrids 129
5.4 New Evidence of Cell Fusion in MM 130
5.4.1 Increased Expression of Fusogenic Proteins 130
5.4.2 Osteoclast Transdifferentiation of Dendritic Cells 130
5.4.3 Functional Osteoclast-Like Activity of Malignant Plasma Cells 132
5.5 Conclusion 133
References 133
6 Cell Fusion Hypothesis of the Cancer Stem Cell 137
6.1 Introduction 137
6.2 Cell Fusion: A Hidden Force in Cancer Progression 138
6.3 CSCs: A Conceptual Advance in Cancer Biology 139
6.4 The Cell Fusion Hypothesis of CSCs 141
6.5 Conclusions 144
References 144
7 Expression of Macrophage Antigens by Tumor Cells 149
7.1 Introduction 149
7.2 Macrophage Antigen CD14 150
7.3 Macrophage Antigen CD68 151
7.4 Macrophage Antigen MAC387 151
7.5 Macrophage Antigen CD163 151
7.6 CD163 Expression in Breast Cancer 153
7.7 CD163 Expression in Colorectal Cancer 153
7.8 CD163 and CD68 Expression in Malignant Melanoma 153
7.9 Macrophage Antigen DAP12 155
7.10 Conclusions 156
References 156
8 Leukocyte-Cancer Cell Fusion: Initiator of the Warburg Effect in Malignancy? 159
8.1 Introduction and Background 159
8.2 Macrophage-Tumor Cell Associations: The Scene of the Crime? 160
8.2.1 Fusion-Induced Aneuploidy 161
8.2.2 Macrophage-Melanoma Fusion In Vitro Generates Altered Gene Expression and a Metastatic Phenotype In Vivo 162
8.2.3 Macrophage-Melanoma Fusion Hybrids Exhibit Up-Regulated Chemotaxis In Vitro 163
8.2.4 SPARC 165
8.2.5 GnT-V and ß1,6-Branched Oligosaccharides 165
8.2.6 Cell Surface Expression of Lysosome Associated Protein-1 (LAMP-1) 165
8.3 Coarse Melanin and Autophagy in Experimental Macrophage-Melanoma Hybrids 166
8.3.1 Spontaneous Fusion In Vivo and Autophagy 166
8.3.2 Autophagy and Aerobic Glycolysis in Macrophages and Cancers 169
8.3.3 Autophagy in Macrophages 170
8.3.4 Autophagy in Human Cancers 171
8.3.5 Normal Epidermis 171
8.3.6 Early Melanoma In Situ (MIS) 172
8.3.7 Autophagy in Florid MIS 172
8.3.8 Autophagy in Tumor Progression 174
8.4 Conclusions and Future Directions 175
References 177
9 Cell Fusion, Drug Resistance and Recurrence CSCs 181
9.1 Introduction 181
9.2 Why Are Different CSC Subtypes Required in Cancer Progression? 182
9.3 Recurrence CSCs 183
9.3.1 CSCs Exhibit an Inherent Resistant Towards Radiation and Cytotoxic Compounds 183
9.3.2 Oncogenic Resistance Demands a Novel Type of CSCs: Recurrence CSCs 184
9.3.3 Cell Fusion and the Origin of rCSCs 185
9.3.4 From Which Cell Types May rCSCs Originate? 187
9.4 Conclusions 187
References 188
10 The Role of Microvesicles in Malignancies 191
10.1 Introduction 191
10.2 What are they, these Membrane Vesicles? 192
10.2.1 Nomenclature, Classification 192
10.2.2 Formation, Composition and Detection of MVs 194
10.3 The Role and the Significance of MVs in the Development of Tumor 196
10.4 The Effects of MVs in Tumorigenesis 197
10.4.1 The Effects of MVs on the Survival and the Maintenance of the Tumor 197
10.4.2 The Effects of MVs on Tumor Growth and Metastasis 200
10.4.3 The Effects of MVs From Different Tissues on the Induction of Tumor 201
10.5 MVs and Tumor Therapy 201
10.5.1 Cell Biological Approach: Inhibition of TMV Formation and Release 202
10.5.2 Immunological Strategies: MVs as Vaccines 202
10.5.3 Removal of TMVs from the Patient's Blood 203
10.6 Conclusion 203
References 204
Index 208