Table Of ContentBiomedical Applications of Proteomics
Editedby
Jean-CharlesSanchez
Garry L. Corthals
DenisF. Hochstrasser
BiomedicalApplicationofProteomics
EditedbyJ.-C.Sanchez,G.Corthals,D.F.Hochstrasser
Copyright©2004Wiley-VCHVerlagGmbH&Co.KGaA,Weinheim
ISBN:3-527-30807-5
Related Titles from WILEY-VCH
ReinerWestermeier,TomNaven
Proteomics in Practice
A Laboratory Manual of Proteome Analysis
2002, 318 pages
ISBN3-527-30354-5
JenniferVanEyk, MichaelJ.Dunn(eds.)
Proteomic and Genomic Analysis of Cardiovascular Disease
2003, 396 pages
ISBN3-527-30596-3
StefanLorkowski, PaulCullen(eds.)
Analysing Gene Expression
A Handbook of Methods. Possibilities and Pittfalls
2003, 954 pages
ISBN3-527-30488-6
DevKambhampati (ed.)
Protein Microarray Technology
2003, 256 pages
ISBN3-527-30597-1
Biomedical Applications of Proteomics
Edited by
Jean-Charles Sanchez
Garry L. Corthals
Denis F. Hochstrasser
Editedby (cid:1) This book was carefully produced. Nevertheless,
editors,authorsandpublisherdonotwarrantthe
Dr.Jean-CharlesSanchez informationcontainedthereintobefreeofer-
Dr.GarryL.Corthals rors.Readersareadvisedtokeepinmindthat
Prof.Dr.DenisF.Hochstrasser statements,data,illustrations,proceduraldetails
orotheritemsmayinadvertentlybeinaccurate.
BiomedicalProteomicsResearchGroup
LaboratoireCentraldeChimieClinique
HopitauxUniversitairesdeGenève
24,rueMicheli-du-Crest
LibraryofCongressCardNo.:appliedfor
1211Genève14
Acataloguerecordforthisbookisavailablefrom
Switzerland
theBritishLibrary.
Bibliographicinformationpublished
byDieDeutscheBibliothek
DieDeutscheBibliothekliststhispublication
intheDeutscheNationalbibliografie;detailed
bibliographicdataisavailableintheInternetat
<http://dnb.ddb.de>.
©2004WILEY-VCHVerlagGmbH&Co.KGaA,
Weinheim
Allrightsreserved(includingthoseoftranslation
inotherlanguages).Nopartofthisbookmaybe
reproducedinanyform–byphotoprinting,micro-
film,oranyothermeans–nortransmittedor
translatedintomachinelanguagewithoutwritten
permissionfromthepublishers.Registerednames,
trademarks,etc.usedinthisbook,evenwhennot
specificallymarkedassuch,arenottobeconside-
redunprotectedbylaw.
PrintedintheFederalRepublicofGermany
Printedonacid-freepaper
Coverdesign SCHULZGrafik-Design,
Fußgönheim
Composition K+VFotosatzGmbH,Beerfelden
Printing betz-druckGmbH,Darmstadt
Bookbinding Litges&DopfBuchbindereiGmbH,
Heppenheim
ISBN 3-527-30807-5
Toour families at home...
Anne-Catherine, Christiane and Hélène
Jule, Kevin, Lucile,Michael, Rory, Sandrine and Virginie
...and to our BPRG family.
BiomedicalApplicationofProteomics
EditedbyJ.-C.Sanchez,G.Corthals,D.F.Hochstrasser
Copyright©2004Wiley-VCHVerlagGmbH&Co.KGaA,Weinheim
ISBN:3-527-30807-5
VII
Contents
ListofContributors XVII
Abbreviations XXV
Introduction 1
DenisF. Hochstrasser, Garry L. Corthals, and Jean-CharlesSanchez
PartI AspectsinBiomedical Research 5
1 ProteomicsinBiomedicine –ATool,aScience,oranArt? 7
Marc A.Reymond
1.1 Introduction 7
1.2 Diagnosisand Prognosis:an Oxymoron 8
1.3 The Dimensionsof Prognosis 9
1.4 Protein Technologies,Diagnosis,and Prognosis 10
1.5 Individual Protein Patterns in Clinical Practice 10
1.6 New ResearchTools,Old Problems 11
1.7 What isHuman Material? 11
1.8 Using Human Tissuein Biomedical Research– Potential Pitfalls 12
1.9 Informed Consent 12
1.10 Specificity ofProteomicsStudies 14
1.11 Conclusionand Summary 14
1.12 Further Reading 15
PartII Blood Vessels 17
2 Antibody-based VascularTargeting:ProteomicTechniques
fortheIdentification andQuantification ofMembraneProteins
onEndothelialCells 19
SimoneScheurer, Jascha-NikolaiRybak, ChristophRoesli,Giuliano Elia,
and Dario Neri
2.1 Introduction 19
2.2 Vascular Targeting 20
BiomedicalApplicationofProteomics
EditedbyJ.-C.Sanchez,G.Corthals,D.F.Hochstrasser
Copyright©2004Wiley-VCHVerlagGmbH&Co.KGaA,Weinheim
ISBN:3-527-30807-5
VIII Contents
2.2.1 Angiogenesis 20
2.2.2 Angiogenesis-relatedDisorders 21
2.2.3 Markersof Angiogenesis 23
2.2.4 Ligand-basedVascularTargeting 24
2.3 Technologiesforthe Quantitation of MembraneProteinsin Different
Cell Types 25
2.3.1 Gel-basedQuantitative Profilingof MembraneProteins 25
2.3.2 Gel-independent Quantitative Profiling ofMembraneProteins 29
2.4 ModelSystems forthe Identification ofVascularTargets 32
2.4.1 In vitro ModelSystems forthe Study ofGeneExpressionin Response
to Environmental Changes 32
2.4.2 In vivo ModelSystems forthe Identification of VascularTargets 33
2.5 Conclusions 35
2.6 Acknowledgements 35
2.7 References 36
3 Vasculature,VascularDisease,andAtherosclerosis 39
ElisabettaGianazza and Ivano Eberini
3.1 Introduction 39
3.2 Protein CompositionofHuman Aorta in Atherosclerosis–
Ex vivo Studies 41
3.2.1 Cellular Proteins 41
3.2.2 Infiltrating Proteins 42
3.3 Protein CompositionofHuman Aorta in Atherosclerosis–
In vitro Studies 44
3.4 Lipoproteinsand Apolipoproteinsas DiseaseFactors 45
3.4.1 Typing of Apolipoprotein E Phenotype in Humans 45
3.4.2 Studiesin Transgenic orKnockout Mice 45
3.5 Pathogenetic Mechanisms 47
3.6 End Pathologies: Myocardialand CerebralInfarction 48
3.7 Surgical Treatments 49
3.8 Pharmacological and Dietary Treatments 49
3.9 Animal Modelsof Atherosclerosisand its Complications 51
3.10 Conclusions 52
3.11 Acknowledgements 52
3.12 References 53
4 Discovery ofNewDiagnostic MarkersofStroke 57
LaureAllard,DenisF. Hochstrasser, and Jean-CharlesSanchez
4.1 Introduction 57
4.2 Stroke Features 57
4.2.1 Brain Anatomy 57
4.2.2 CerebrovascularBloodCirculation 59
4.2.3 Aetiology and Pathology ofStroke 59
4.2.4 Pathophysiology – DifferentTypes of Stroke 59
Contents IX
4.2.5 Epidemiology 60
4.2.6 Treatment 61
4.3 Current Diagnosisof Stroke 61
4.3.1 Physician’s Evaluation 62
4.3.2 Imaging 62
4.3.3 Lumbar Puncture 62
4.3.4 BiochemicalMarkers ofStroke 63
4.4 Proteomic-basedApproach for the Discoveryof Early Diagnostic
Stroke Markers 63
4.4.1 One-dimensionalGel Electrophoresis 64
4.4.2 Two-dimensionalGel Electrophoresis 66
4.4.3 SELDI-TOF 69
4.5 Conclusions 70
4.6 Acknowledgements 71
4.7 References 71
PartIII Cancer 73
5 UnravellingBiological PathwaysandtheIdentification ofClinicalMarkers
andTargetsinRenalCancer 75
RosamondeE. Banksand PeterJ. Selby
5.1 Renal Cancer – The Clinical Perspective 75
5.1.1 Epidemiology 75
5.1.2 Current Clinical Approachesand Clinical Challenges 76
5.1.3 Immunotherapy for Renal Cancer 78
5.1.4 Existing MarkersorTherapeutic Targets UndergoingClinical
Evaluation 79
5.2 ProteomicStudies 80
5.2.1 Tissue-basedStudies 81
5.2.2 Primary and EstablishedCell Lines 87
5.2.3 Biological Fluids 88
5.3 Conclusions 90
5.4 References 91
6 HeatShockProtein27inCancer 97
CeciliaSarto, FulvioMagni, CristinaValsecchi,and Paolo Mocarelli
6.1 Introduction 97
6.2 Genomic Aspects 97
6.3 Structure 98
6.4 Functions 99
6.5 HSP27 Expressionin Cancer 101
6.6 Post-translationalModification and ProteomicTools 102
6.6.1 Phosphorylation 106
6.6.2 S-Thiolation, Oxidation, and Others 106
6.7 Perspectives 107
X Contents
6.8 Acknowledgements 107
6.9 References 108
7 Proteomic ApproachesforBiomarkerDiscovery inColorectal Cancer 111
Richard J. Simpsonand Donna S. Dorow
7.1 Introduction and Background toColorectalCancer 111
7.2 MolecularBasisof ColorectalCancer: Tumorigenesis
isa Multistep Process 112
7.3 The CaseforEarly Detection:CRCisTreatableif DetectedEarly 114
7.4 Approachesto Biomarker Discovery 116
7.4.1 UseofELISAs to DetectCRC 119
7.4.2 Two-dimensionalGel Electrophoresis 120
7.4.3 One-dimensionalSodium DodecylSulfate-Polyacrylamide
Gel Electrophoresis(SDS-PAGE) Plasma MembraneProteome 123
7.4.4 Multidimensional Protein Identification Technologies 124
7.4.5 ProteomicPattern Diagnostics 125
7.4.6 Protein Microarrays 126
7.4.7 ProteomicApproachesforIdentifyingTumor-specificAutoantigens 127
7.5 Conclusions 127
7.6 References 128
8 ClinicalProteomics: OvarianCancer 133
AyodeleA. Alaiya
8.1 Introduction 133
8.2 General Background 135
8.2.1 OvarianCancer 135
8.2.2 OvarianTumorMarkers 137
8.2.3 ScreeningMethodsandDiagnosticDifficultiesinOvarianTumors 139
8.2.4 Treatment and Prognosisof OvarianTumors 139
8.3 Cancer Proteomics 140
8.3.1 Protein Profiling and Cancer 140
8.3.2 RNA ExpressionAnalysis in CancerCells: Promisesand Pitfalls 141
8.3.3 Potentials and Limitations ofCurrent Protein Profiling
Technologies 142
8.3.4 Unravelling Tumor Complexity Prior to ProteomeAnalysis 143
8.3.5 The Future of Clinical Proteomics:Challenges and Opportunities 144
8.4 Short OverviewofOvarian Cancer Proteomics 145
8.4.1 The PromiseofProteomicsin OvarianCancerDiagnostics 145
8.4.2 Analysis ofTissueSamples 146
8.4.3 Analysis ofSerum Samples 147
8.4.4 DiseasePrognosisand Protein ExpressionData 148
8.5 Acknowledgements 150
8.6 References 151
Contents XI
9 ProteinExpressionProfilingAnalysisinHematopoietic StemCells:
PhenotypicCharacterization ofMesenchymalStemCells 155
JuanAntonio 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 Horizonsin Stem Cell Biology 157
9.2.3 Current and Future Applications of the Stem Cell Technology 157
9.2.4 Stemnessand Stem Cell-associatedGenetic Programs 159
9.3 Proteomics 160
9.3.1 Differential Display via Two-DimensionalGel Electrophoresis 162
9.3.2 Protein Identification 164
9.3.3 Differential Proteomics 164
9.3.4 Protein Profiling 165
9.4 ProteomicAnalysis ofMSCs 165
9.5 Acknowledgements 169
9.6 References 170
10 Lymphoblastoid andLymphoma Cells 173
Raymonde Joubert-Caron, Didier Lutomski,and MichelCaron
10.1 Introduction 173
10.2 Experimental Models 174
10.2.1 Experimental Procedures 174
10.3 Studiesof Protein-pattern Changes Following Treatment
with AZC 175
10.3.1 Soluble Protein-pattern Changes Induced by AZC Treatment 177
10.3.2 Membrane-associatedProtein Pattern Changes Induced
by AZC Treatment 180
10.4 ProteomicStudy ofGal1-mediated B Cell Apoptosis 183
10.4.1 Identification ofthe MajorGal1-binding MembraneGlycoprotein 184
10.4.2 KineticsofModificationofPhosphorylation ofthe Protein Tyrosine
KinaseLyn 184
10.5 Lymphoblastoid and Lymphoma Cells 2-DE Database 186
10.6 References 188
PartIV Pharmaco-toxicology 189
11 Chemoresistance inCancerCells 191
JuliaPoland, DirkSchadendorf, HermannLage,and Pranav Sinha
11.1 Introduction 191
11.2 Two-dimensionalElectrophoresisMaps of GastricCancer, Pancreatic
Cancer, and Melanoma 192
11.2.1 GastricCancer 192
11.2.2 PancreaticCancer 194
11.2.3 Melanoma 196
