Biomedical applications of proteomics

List of Contributors XVII Abbreviations XXV Introduction 1 Denis F. Hochstrasser, Garry L. Corthals, and Jean-Charles Sanchez Part I Aspects in Biomedical Research 5 1 Proteomics in Biomedicine – A Tool, a Science, or an Art? 7 Marc A. Reymond 1.1 Introduction 7 1.2 Diagnosis and Prognosis: an Oxymoron 8 1.3 The Dimensions of Prognosis 9 1.4 Protein Technologies, Diagnosis, and Prognosis 10 1.5 Individual Protein Patterns in Clinical Practice 10 1.6 New Research Tools, Old Problems 11 1.7 What is Human Material? 11 1.8 Using Human Tissue in Biomedical Research – Potential Pitfalls 12 1.9 Informed Consent 12 1.10 Specificity of Proteomics Studies 14 1.11 Conclusion and Summary 14 1.12 Further Reading 15 Part II Blood Vessels 17 2 Antibody-based Vascular Targeting: Proteomic Techniques for the Identification and Quantification of Membrane Proteins on Endothelial Cells 19 Simone Scheurer, Jascha-Nikolai Rybak, Christoph Roesli, Giuliano Elia, and Dario Neri 2.1 Introduction 19 2.2 Vascular Targeting 20 VII Contents Biomedical Application of Proteomics Edited by J.-C. Sanchez, G. Corthals, D.F. Hochstrasser Copyright © 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30807-5 2.2.1 Angiogenesis 20 2.2.2 Angiogenesis-related Disorders 21 2.2.3 Markers of Angiogenesis 23 2.2.4 Ligand-based Vascular Targeting 24 2.3 Technologies for the Quantitation of Membrane Proteins in Different Cell Types 25 2.3.1 Gel-based Quantitative Profiling of Membrane Proteins 25 2.3.2 Gel-independent Quantitative Profiling of Membrane Proteins 29 2.4 Model Systems for the Identification of Vascular Targets 32 2.4.1 In vitro Model Systems for the Study of Gene Expression in Response to Environmental Changes 32 2.4.2 In vivo Model Systems for the Identification of Vascular Targets 33 2.5 Conclusions 35 2.6 Acknowledgements 35 2.7 References 36 3 Vasculature, Vascular Disease, and Atherosclerosis 39 Elisabetta Gianazza and Ivano Eberini 3.1 Introduction 39 3.2 Protein Composition of Human Aorta in Atherosclerosis – Ex vivo Studies 41 3.2.1 Cellular Proteins 41 3.2.2 Infiltrating Proteins 42 3.3 Protein Composition of Human Aorta in Atherosclerosis – In vitro Studies 44 3.4 Lipoproteins and Apolipoproteins as Disease Factors 45 3.4.1 Typing of Apolipoprotein E Phenotype in Humans 45 3.4.2 Studies in Transgenic or Knockout Mice 45 3.5 Pathogenetic Mechanisms 47 3.6 End Pathologies: Myocardial and Cerebral Infarction 48 3.7 Surgical Treatments 49 3.8 Pharmacological and Dietary Treatments 49 3.9 Animal Models of Atherosclerosis and its Complications 51 3.10 Conclusions 52 3.11 Acknowledgements 52 3.12 References 53 4 Discovery of New Diagnostic Markers of Stroke 57 Laure Allard, Denis F. Hochstrasser, and Jean-Charles Sanchez 4.1 Introduction 57 4.2 Stroke Features 57 4.2.1 Brain Anatomy 57 4.2.2 Cerebrovascular Blood Circulation 59 4.2.3 Aetiology and Pathology of Stroke 59 4.2.4 Pathophysiology – Different Types of Stroke 59 VIII Contents 4.2.5 Epidemiology 60 4.2.6 Treatment 61 4.3 Current Diagnosis of Stroke 61 4.3.1 Physician’s Evaluation 62 4.3.2 Imaging 62 4.3.3 Lumbar Puncture 62 4.3.4 Biochemical Markers of Stroke 63 4.4 Proteomic-based Approach for the Discovery of Early Diagnostic Stroke Markers 63 4.4.1 One-dimensional Gel Electrophoresis 64 4.4.2 Two-dimensional Gel Electrophoresis 66 4.4.3 SELDI-TOF 69 4.5 Conclusions 70 4.6 Acknowledgements 71 4.7 References 71 Part III Cancer 73 5 Unravelling Biological Pathways and the Identification of Clinical Markers and Targets in Renal Cancer 75 Rosamonde E. Banks and Peter J. Selby 5.1 Renal Cancer – The Clinical Perspective 75 5.1.1 Epidemiology 75 5.1.2 Current Clinical Approaches and Clinical Challenges 76 5.1.3 Immunotherapy for Renal Cancer 78 5.1.4 Existing Markers or Therapeutic Targets Undergoing Clinical Evaluation 79 5.2 Proteomic Studies 80 5.2.1 Tissue-based Studies 81 5.2.2 Primary and Established Cell Lines 87 5.2.3 Biological Fluids 88 5.3 Conclusions 90 5.4 References 91 6 Heat Shock Protein 27 in Cancer 97 Cecilia Sarto, Fulvio Magni, Cristina Valsecchi, and Paolo Mocarelli 6.1 Introduction 97 6.2 Genomic Aspects 97 6.3 Structure 98 6.4 Functions 99 6.5 HSP27 Expression in Cancer 101 6.6 Post-translational Modification and Proteomic Tools 102 6.6.1 Phosphorylation 106 6.6.2 S-Thiolation, Oxidation, and Others 106 6.7 Perspectives 107 Contents IX 6.8 Acknowledgements 107 6.9 References 108 7 Proteomic Approaches for Biomarker Discovery in Colorectal Cancer 111 Richard J. Simpson and Donna S. Dorow 7.1 Introduction and Background to Colorectal Cancer 111 7.2 Molecular Basis of Colorectal Cancer: Tumorigenesis is a Multistep Process 112 7.3 The Case for Early Detection: CRC is Treatable if Detected Early 114 7.4 Approaches to Biomarker Discovery 116 7.4.1 Use of ELISAs to Detect CRC 119 7.4.2 Two-dimensional Gel Electrophoresis 120 7.4.3 One-dimensional Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) Plasma Membrane Proteome 123 7.4.4 Multidimensional Protein Identification Technologies 124 7.4.5 Proteomic Pattern Diagnostics 125 7.4.6 Protein Microarrays 126 7.4.7 Proteomic Approaches for Identifying Tumor-specific Autoantigens 127 7.5 Conclusions 127 7.6 References 128 8 Clinical Proteomics: Ovarian Cancer 133 Ayodele A. Alaiya 8.1 Introduction 133 8.2 General Background 135 8.2.1 Ovarian Cancer 135 8.2.2 Ovarian Tumor Markers 137 8.2.3 Screening Methods and Diagnostic Difficulties in Ovarian Tumors 139 8.2.4 Treatment and Prognosis of Ovarian Tumors 139 8.3 Cancer Proteomics 140 8.3.1 Protein Profiling and Cancer 140 8.3.2 RNA Expression Analysis in Cancer Cells: Promises and Pitfalls 141 8.3.3 Potentials and Limitations of Current Protein Profiling Technologies 142 8.3.4 Unravelling Tumor Complexity Prior to Proteome Analysis 143 8.3.5 The Future of Clinical Proteomics: Challenges and Opportunities 144 8.4 Short Overview of Ovarian Cancer Proteomics 145 8.4.1 The Promise of Proteomics in Ovarian Cancer Diagnostics 145 8.4.2 Analysis of Tissue Samples 146 8.4.3 Analysis of Serum Samples 147 8.4.4 Disease Prognosis and Protein Expression Data 148 8.5 Acknowledgements 150 8.6 References 151 X Contents 9 Protein Expression Profiling Analysis in Hematopoietic Stem Cells: Phenotypic Characterization of Mesenchymal Stem Cells 155 Juan Antonio López, Antonio Bernad, and Juan Pablo Albar 9.1 Introduction 155 9.2 Mesenchymal Stem Cells 155 9.2.1 Stem Cell Definition Criteria 156 9.2.2 New Horizons in Stem Cell Biology 157 9.2.3 Current and Future Applications of the Stem Cell Technology 157 9.2.4 Stemness and Stem Cell-associated Genetic Programs 159 9.3 Proteomics 160 9.3.1 Differential Display via Two-Dimensional Gel Electrophoresis 162 9.3.2 Protein Identification 164 9.3.3 Differential Proteomics 164 9.3.4 Protein Profiling 165 9.4 Proteomic Analysis of MSCs 165 9.5 Acknowledgements 169 9.6 References 170 10 Lymphoblastoid and Lymphoma Cells 173 Raymonde Joubert-Caron, Didier Lutomski, and Michel Caron 10.1 Introduction 173 10.2 Experimental Models 174 10.2.1 Experimental Procedures 174 10.3 Studies of Protein-pattern Changes Following Treatment with AZC 175 10.3.1 Soluble Protein-pattern Changes Induced by AZC Treatment 177 10.3.2 Membrane-associated Protein Pattern Changes Induced by AZC Treatment 180 10.4 Proteomic Study of Gal1-mediated B Cell Apoptosis 183 10.4.1 Identification of the Major Gal1-binding Membrane Glycoprotein 184 10.4.2 Kinetics of Modification of Phosphorylation of the Protein Tyrosine Kinase Lyn 184 10.5 Lymphoblastoid and Lymphoma Cells 2-DE Database 186 10.6 References 188 Part IV Pharmaco-toxicology 189 11 Chemoresistance in Cancer Cells 191 Julia Poland, Dirk Schadendorf, Hermann Lage, and Pranav Sinha 11.1 Introduction 191 11.2 Two-dimensional Electrophoresis Maps of Gastric Cancer, Pancreatic Cancer, and Melanoma 192 11.2.1 Gastric Cancer 192 11.2.2 Pancreatic Cancer 194 11.2.3 Melanoma 196 Contents XI 11.3 Evaluation of the 2-DE Protein Maps 197 11.3.1 Chemoresistance Overview 197 11.3.2 Mechanisms of Drug Resistance 198 11.3.3 Differentially Expressed Proteins in Drug-resistant Cancer Cells 200 11.4 Conclusions 202 11.5 References 203 12 Diabetes Mellitus: Complex Molecular Alterations 205 Gerhard Schmid and Jean-Charles Sanchez 12.1 Introduction 205 12.1.1 Glucose Homeostasis 206 12.1.2 The Islets of Langerhans 207 12.1.3 The Pancreatic Beta-Cell 208 12.2 Molecular Alterations in the Pathogenesis of T1DM and T2DM 209 12.2.1 Type 1 Diabetes Mellitus 209 12.2.2 Type 2 Diabetes Mellitus 209 12.3 The Treatment of Diabetes Mellitus 215 12.4 Proteomics: a Global Approach to the Study of Diabetes Mellitus 216 12.4.1 Type 1 Diabetes Mellitus 217 12.4.2 Type 2 Diabetes Mellitus 217 12.5 Conclusions 220 12.6 References 221 Part V Infectious Diseases 225 13 Proteome Approach to Infectious Diseases: Acute-phase Proteins and Antibody Profiles as Diagnostic Indicators in Human Plasma 227 Luca Bini, Sabrina Liberatori, and Vitaliano Pallini 13.1 Introduction 227 13.2 Electrophoretic Map of Acute-phase Response Proteins 228 13.3 Clinical Monitoring of APR Proteins by 2-DE 230 13.4 Chlamydia trachomatis Immunoproteome 232 13.5 Human Humoral Immune Response to Chlamydia trachomatis Infections 234 13.6 Genetic Susceptibility to Chlamydia trachomatis Determines the Outcome of the Disease: Data from a Mouse Model 236 13.7 Conclusions 240 13.8 References 242 14 Proteomic Studies of Human Lymphocytes: New Insights into HIV Lymphocyte Infection? 245 Françoise Vuadens, David Crettaz, Amalio Telenti, Manfredo Quadroni, Michel A. Duchosal, Philippe Schneider, and Jean-Daniel Tissot 14.1 Introduction 245 14.1.1 The Lymphocytes 245 XII Contents 14.1.2 Human Immunodeficiency Virus and the Lymphocytes 247 14.2 Proteomics of Lymphocytes 248 14.2.1 Isolation of Lymphocytes 248 14.2.2 Two-dimensional Electrophoresis and Mass Spectrometry 248 14.3 Results and Discussion 249 14.3.1 A (Preliminary) Reference Lymphocyte Map (IPG: 3–10 NL) 249 14.3.2 Differential Expression of Proteins in CD4, CD8, and CD 19 Lymphocytes 249 14.3.3 Applications in HIV Physiopathology 258 14.4 Summary 259 14.5 References 260 15 Modifications of Host Cell Proteomes Induced by Herpes Simplex Virus Type 1 263 Anna Greco, Yohann Couté, Stéphane Giraud, and Jean-Jacques Diaz 15.1 Introduction 263 15.2 Modifications of Host Cell Gene Expression: a Proteomic Approach 266 15.2.1 Cellular Proteins Escape the Virally Induced Shut-off of Protein Synthesis 267 15.2.2 Ribosome Biogenesis Persists in HSV-1-infected Cells 269 15.3 Nucleus and Lytic HSV-1 Infection 274 15.3.1 Functional Organization of the Cell Nucleus 274 15.3.2 HSV-1-induced Modifications of the Host Cell Nucleus 276 15.3.3 Distribution of HSV-1 Proteins Within Different Nuclear Domains 278 15.4 Conclusions 280 15.5 References 281 16 Francisella tularensis 285 Jirí Stulík, Martin Hubálek, Lenka Hernychová, Jana Havlasová, Juraj Lenco, Ales Macela, Igor Golovliov, and Anders Sjöstedt 16.1 Intracellular Pathogen Francisella tularensis 285 16.1.1 Subtypes of F. tularensis 285 16.1.2 The Major Objectives of Proteome Studies of F. tularensis 286 16.2 Construction of Two-dimensional Electrophoresis (2-DE) Reference Protein Maps of Non-virulent and Highly Virulent F. tularensis Strains 287 16.3 Comparative Proteome Analysis of F. tularensis Subspecies 290 16.4 Application of MALDI-TOF Mass Spectrometry for Typing of F. tularensis 305 16.5 Identification of Tularemic Antigens Recognized by Sera Collected from Naturally Infected Individuals 310 16.6 Conclusions 311 16.7 Acknowledgements 312 16.8 References 312 Contents XIII Part VI Central Nervous System 315 17 Proteomics in Clinical Neurosciences 317 Pierre R. Burkhard and Jean-Charles Sanchez 17.1 Introduction 317 17.2 Nervous System-related Samples 318 17.2.1 Brain Tissue 319 17.2.2 Cerebrospinal Fluid 322 17.3 Proteomics Studies in Neurological Diseases 327 17.3.1 Brain Tumor 328 17.3.2 Multiple Sclerosis 329 17.3.3 Stroke and Cerebrovascular Diseases 331 17.3.4 Creutzfeldt-Jakob Disease 333 17.3.5 Alzheimer’s Disease and Related Dementias 334 17.3.6 Parkinson’s Disease 335 17.3.7 Huntington’s Disease 336 17.3.8 Miscellaneous 336 17.4 Conclusions 337 17.5 Acknowledgements 337 17.6 References 337 18 Human Cerebrospinal Fluid Pia Davidsson and Michael G. Harrington 341 18.1 Introduction 341 18.2 Experimental Design 342 18.2.1 Sample Collection and Preparation 343 18.3 Two-dimensional Gels of CSF, with Protein Identification by Antibodies, Edman Degradation Chemistry, MALDI/MS or LC/MS of Individual “Spots” 343 18.3.1 Prefractionation of CSF Prior to 2-DE 346 18.3.2 Two-dimensional Liquid-phase Electrophoresis and Other LC-coupled MS Approaches 347 18.4 CSF Proteomic Applications in Central Nervous System Diseases 348 18.5 Future Challenges 349 18.6 References 351 19 Proteomic Applications for Molecular Assessment of Alzheimer’s Disease 355 Odile Carrette, Pierre R. Burkhard, Denis F. Hochstrasser, and Jean-Charles Sanchez 19.1 Introduction 355 19.2 Two-dimensional Gel Electrophoresis Studies 356 19.2.1 General Screening Studies 357 19.2.2 Tau Protein 358 19.2.3 Amyloid Precursor Protein 359 XIV Contents 19.2.4 Oxidative Stress and Antioxidant Response 361 19.3 SELDI 362 19.3.1 Amyloid Beta Peptide Analyzed by SELDI 362 19.3.2 Screening of AD with SELDI on a Strong Anionic Exchange Surface 363 19.3.3 Screening of AD, FTD, LBD, and VD with SELDI on a Weak Cationic Exchange (WCX2) Surface 367 19.4 Conclusions 367 19.5 Acknowledgements 369 19.6 References 369 Part VII Mass Spectrometry and Bioinformatics 371 20 MALDI-MS Imaging in Biomedical Research 373 Markus Stoeckli and Terry B. Farmer 20.1 Introduction 373 20.1.1 Background 374 20.2 Methods 376 20.2.1 Tissue Preparation Technique 376 20.3 Applications 383 20.3.1 Beta-amyloid Imaging 384 20.4 Conclusions 387 20.5 References 388 21 Protein Variations: Resources and Tools 389 Yum Lina Yip, Maria Livia Famiglietti, Elisabeth Gasteiger, and Amos Bairoch 21.1 Introduction 389 21.2 Medical Protein Annotation 390 21.3 Databases 391 21.3.1 Central Databases 392 21.3.2 Specialized Databases 394 21.3.3 The Swiss-Prot Protein Knowledgebase and Information on Disease and Sequence Variations 401 21.3.4 Techniques of Search 409 21.3.5 Challenges for Databases 410 21.4 Analysis Tools in the Context of Protein Variants 411 21.4.1 Proteomic Tools for Protein Identification and the Characterization of Variants 412 21.4.2 Tools for Analyzing and/or Predicting the Effects of Protein Variants 414 21.5 Conclusions 419 21.6 References 419 Subject Index 423 Contents XV