Cancer Metabolism: Methods and Protocols

491 Pages·2019·13.403 MB·English

by  Majda Haznadar

Methods in
Molecular Biology 1928
Majda Haznadar Editor
Cancer
Metabolism
Methods and Protocols
M M B
ETHODS IN OLECULAR IO LO GY
SeriesEditor
JohnM.Walker
School of Lifeand MedicalSciences
University ofHertfordshire
Hatfield, Hertfordshire,AL109AB,UK
Forfurther volumes:
http://www.springer.com/series/7651
Cancer Metabolism
Methods and Protocols
Edited by
Majda Haznadar
National Cancer Institute, North Bethesda, MD, USA
Editor
MajdaHaznadar
NationalCancerInstitute
NorthBethesda,MD,USA
ISSN1064-3745 ISSN1940-6029 (electronic)
MethodsinMolecularBiology
ISBN978-1-4939-9026-9 ISBN978-1-4939-9027-6 (eBook)
https://doi.org/10.1007/978-1-4939-9027-6
LibraryofCongressControlNumber:2018966343
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Preface
In 1956, Otto Heinrich Warburg publishedseminal research wherein hedescribed a novel
processbywhichcancercellssurvive,theprocessofrelyingonaerobicglycolysisratherthan
oxidativephosphorylation,usedbynormaldifferentiatedcells.Thisnovelprocesshasbeen
termed“theWarburgeffect.”Sincethen,researchershavebeenworkingondiscerninghow
cancer cells adapt some and bypass other metabolic processes, in order to fulfill their high
energy needs. Some more recent studies have also illuminated processes by which cancer
cells utilize external energy sources to generate building blocks required for their high
energy turnover. This volume of Methods in MolecularBiology series isdesigned to provide
commonexperimentalapproachesinstudiesdesignedtoilluminatevariousprocessesstud-
iedincancermetabolism.Eachchapteropensupwiththetheorybehindthemethodbeing
described. Every laboratory protocol chapter includes chemicals and reagents necessary to
carry out a given protocol. Each methods section of laboratory protocol chapters contains
detailed step-by-step description for successful completion of that method. The book is
divided into three compartments. The first part of the book focuses on specific protocols
commonly utilized in cancer metabolism studies, such as protocols comprising stable
isotope labeling methods, protocols for studying glycolysis, gluconeogenesis, and mito-
chondrial metabolism. This portion of the book also includes chapters containingimaging
toolstostudycellularmetabolism,aswellasdescriptionsoftoolstostudymacrophagesand
autophagy and their relevance in cancer. The second part of the book is geared toward
describingmethodsusedforgeneratinghypothesesandidentifyingcancermarkers,suchas
massspectrometry-andNMR-basedprofilingtools,aswellasaprotocolwithadescription
of tools for studying the human microbiome. This portion of the book also contains two
protocolsutilizingSeahorse,acommonlyusedlaboratoryplatformforstudyingcellmetab-
olism. The last part of the book is designed to describe an overview of vital and actively
researchedtopicsinthefieldofcancermetabolism,aswellascomputationalmethodological
approaches. We hope that this book will become an essential compilation of protocols
utilizedinmanylaboratoriesthatconductthistypeofresearch.
NorthBethesda,MD,USA MajdaHaznadar
v
Contents
Preface ..................................................................... v
Contributors................................................................. ix
1 MetabolicLabelingofCulturedMammalianCellsforStable
Isotope-ResolvedMetabolomics:PracticalAspectsofTissueCulture
andSampleExtraction................................................... 1
DanielR.Crooks,TeresaW.-M.Fan,andW.MarstonLinehan
2 ImagingCancerMetabolismwithPositronEmission
Tomography(PET) ..................................................... 29
TimothyH.WitneyandDavidY.Lewis
3 RadioluminescenceMicroscopy:AQuantitativeMethod
forRadioisotopicImagingofMetabolicFluxesinLivingCancerCells......... 45
DebantiSenguptaandGuillemPratx
4 Useof13C 15N -Serineor13C 15N -MethionineforStudying
3 1 5 1
MethylationDynamicsinCancerCellMetabolismandEpigenetics ........... 55
AliceC.Newman,ChristiaanF.Labuschagne,KarenH.Vousden,
andOliverD.K.Maddocks
5 MeasurementofMitochondrialMembranePotentialwiththeFluorescent
DyeTetramethylrhodamineMethylEster(TMRM)......................... 69
SarahCreedandMatthewMcKenzie
6 AssessmentofStabilizationandActivityoftheHIFsImportant
forHypoxia-InducedSignallinginCancerCells ............................ 77
DavidKung-ChunChiu,MistyShuoZhang,AkiPui-WahTse,andCarmen
Chak-LuiWong
7 DeterminationofPolarizationofResidentMacrophages
andTheirEffectontheTumorMicroenvironment.......................... 101
IoannisS.PaterasandTomerCooks
8 QuantitationofMacropinocytosisinCancerCells........................... 113
KoenM.O.Galenkamp,BasheerAlas,andCosimoCommisso
9 IntegratedAnalysisofAcetyl-CoAandHistoneModificationvia
MassSpectrometrytoInvestigateMetabolicallyDrivenAcetylation ........... 125
SimoneSidoli,SophieTrefely,BenjaminA.Garcia,andAlessandroCarrer
10 MethodstoMeasureAutophagyinCancerMetabolism ..................... 149
NataliavonMuhlinen
11 LipidomicAnalysisofCancerCellandTumorTissues....................... 175
RamizIslamSkandSoumenKantiManna
12 MassSpectrometry-BasedProfilingofMetabolitesinHumanBiofluids........ 205
TanushreeChakrabortyandSoumenKantiManna
vii
viii Contents
13 GasChromatography-MassSpectrometryandAnalysis
oftheSerumMetabolomicProfileThroughExtraction
andDerivatizationofPolarMetabolites ................................... 235
JodiRattner,FarshadFarshidfar,andOliverF.Bathe
14 MetaboliteProfilingofClinicalCancerBiofluidSamples
byNMRSpectroscopy................................................... 251
BeataMickiewicz,M.EricHyndman,andHansJ.Vogel
15 AssessmentofMetabolicSignatureforCancerDiagnosisUsing
DesorptionElectrosprayIonizationMassSpectrometricImaging............. 275
ShibdasBanerjeeandSoumenKantiManna
16 CompositionalAnalysisoftheHumanMicrobiomeinCancerResearch ....... 299
ElisaMorales,JunChen,andK.LeighGreathouse
17 AssessingMetabolicDysregulationinMuscleDuringCachexia............... 337
MyriamY.Hsu,PaoloE.Porporato,andElisabethWyart
18 UsingSeahorseMachinetoMeasureOCRandECARinCancerCells ........ 353
JingZhangandQingZhang
19 MetabolicProfilingofLiveCancerTissuesUsingNAD(P)H
FluorescenceLifetimeImaging........................................... 365
ThomasS.Blacker,MichaelD.E.Sewell,GyorgySzabadkai,
andMichaelR.Duchen
20 OverviewofCharacterizingCancerGlycanswithLectin-Based
AnalyticalMethods...................................................... 389
AmandaJ.PearsonandElyssiaS.Gallagher
21 HyperpolarizedMRIforStudyingTumorMetabolism ...................... 409
MikkoI.Kettunen
22 OverviewofGlutamineDependencyandMetabolicRescueProtocols......... 427
ShuoQie,DanHe,andNianliSang
23 IntegrationofMetabolomicsandTranscriptomicstoIdentify
Gene-MetaboliteRelationshipsSpecifictoPhenotype ....................... 441
AndrewPatt,JalalSiddiqui,BofeiZhang,andEwyMathe´
24 BiclusteringAnalysisofCo-regulationPatternsinNuclear-Encoded
MitochondrialGenesandMetabolicPathways.............................. 469
RobertB.Bentham,KevinBryson,andGyorgySzabadkai
25 UsingtheHumanGenome-ScaleMetabolicModelRecon
2forSteady-StateFluxAnalysisofCancerCellMetabolism.................. 479
Lake-EeQuekandNigelTurner
Index ...................................................................... 491
Contributors
BASHEERALAS (cid:1) TumorInitiationandMaintenanceProgram,NCI-DesignatedCancer
Center,SanfordBurnhamPrebysMedicalDiscoveryInstitute,LaJolla,CA,USA
SHIBDASBANERJEE (cid:1) IndianInstituteofScienceEducationandResearchTirupati,Tirupati,
AndhraPradesh,India
OLIVERF.BATHE (cid:1) ArnieCharbonneauCancerInstitute,UniversityofCalgary,Calgary,
AB,Canada;DepartmentofSurgery,TomBakerCancerCenter,UniversityofCalgary,
Calgary,AB,Canada;DepartmentofOncology,TomBakerCancerCenter,Universityof
Calgary,Calgary,AB,Canada
ROBERTB.BENTHAM (cid:1) DepartmentofCellandDevelopmentalBiology,Consortiumfor
MitochondrialResearch,UniversityCollegeLondon,London,UK
THOMASS.BLACKER (cid:1) ResearchDepartmentofCell&DevelopmentalBiology,University
CollegeLondon,London,UK;UCLConsortiumforMitochondrialResearch,University
CollegeLondon,London,UK;DepartmentofPhysics&Astronomy,UniversityCollege
London,London,UK
KEVINBRYSON (cid:1) DepartmentofComputerSciences,UniversityCollegeLondon,London,UK
ALESSANDROCARRER (cid:1) DepartmentofCancerBiology,AbramsonFamilyCancerResearch
Institute,UniversityofPennsylvania,Philadelphia,PA,USA
TANUSHREE CHAKRABORTY (cid:1) BiophysicsandStructuralGenomicsDivision,SahaInstituteof
NuclearPhysics(HBNI),Kolkata,India
JUNCHEN (cid:1) DivisionofBiomedicalStatisticsandInformatics,DepartmentofHealth
SciencesResearch,MayoClinic,Rochester,MN,USA
DAVIDKUNG-CHUNCHIU (cid:1) DepartmentofPathology,QueenMaryHospital,TheUniversity
ofHongKong,Pokfulam,HongKong
COSIMOCOMMISSO (cid:1) TumorInitiationandMaintenanceProgram,NCI-Designated
CancerCenter,SanfordBurnhamPrebysMedicalDiscoveryInstitute,LaJolla,CA,USA
TOMERCOOKS (cid:1) FacultyofHealthSciences,TheShragaSegalDepartmentofMicrobiology,
ImmunologyandGenetics,BenGurionUniversityoftheNegev,BeerSheva,Israel
SARAH CREED (cid:1) MonashMicroImaging,HudsonInstituteofMedicalResearch,Clayton,
VIC,Australia
DANIELR.CROOKS (cid:1) UrologicOncologyBranch,NationalCancerInstitute,National
InstitutesofHealth,Bethesda,MD,USA
MICHAELR.DUCHEN (cid:1) ResearchDepartmentofCell&DevelopmentalBiology,University
CollegeLondon,London,UK;UCLConsortiumforMitochondrialResearch,University
CollegeLondon,London,UK
TERESAW.-M.FAN (cid:1) DepartmentofToxicologyandCancerBiology,Center for
EnvironmentalandSystemsBiochemistry,MarkeyCancerCenter,UniversityofKentucky,
Lexington,KY,USA
FARSHADFARSHIDFAR (cid:1) DepartmentofOncologyandArnieCharbonneauCancerInstitute,
CummingSchoolofMedicine,UniversityofCalgary,Calgary,Canada
KOENM.O.GALENKAMP (cid:1) TumorInitiationandMaintenanceProgram,NCI-Designated
CancerCenter,SanfordBurnhamPrebysMedicalDiscoveryInstitute,LaJolla,CA,USA
ELYSSIAS.GALLAGHER (cid:1) DepartmentofChemistryandBiochemistry,BaylorUniversity,
Waco,TX,USA
ix
x Contributors
BENJAMINA.GARCIA (cid:1) DepartmentofBiochemistryandBiophysics,PerelmanSchoolof
Medicine,EpigeneticsInstitute,UniversityofPennsylvania,Philadelphia,PA,USA
K.LEIGHGREATHOUSE (cid:1) RobbinsCollegeofHealthandHumanSciences,BaylorUniversity,
Waco,TX,USA
DANHE (cid:1) DepartmentofBiology,CollegeofArtsandSciences,DrexelUniversity,
Philadelphia,PA,USA
MYRIAMY.HSU (cid:1) DepartmentofMolecularBiotechnologyandHealthScience,Molecular
BiotechnologyCenter,UniversityofTorino,Torino,Italy
M.ERICHYNDMAN (cid:1) DivisionofUrology,DepartmentofSurgery,SouthernAlbertaInstitute
ofUrology,UniversityofCalgary,Calgary,AB,Canada
RAMIZISLAMSK (cid:1) BiophysicsandStructuralGenomicsDivision,SahaInstituteofNuclear
Physics(HBNI),Kolkata,India
MIKKO I.KETTUNEN (cid:1) A.I.VirtanenforMolecularSciences,UniversityofEasternFinland,
Kuopio,Finland
CHRISTIAANF.LABUSCHAGNE (cid:1) TheFrancisCrickInstitute,London,UK
DAVIDY.LEWIS (cid:1) MolecularImagingLaboratory,CancerResearchUKBeatsonInstitute,
Glasgow,UK;InstituteofCancerSciences,UniversityofGlasgow,Glasgow,UK
W.MARSTONLINEHAN (cid:1) UrologicOncologyBranch,NationalCancerInstitute,National
InstitutesofHealth,Bethesda,MD,USA
OLIVERD.K.MADDOCKS (cid:1) WolfsonWohlCancerResearchCentre,InstituteofCancer
Sciences,UniversityofGlasgow,Glasgow,UK
SOUMENKANTIMANNA (cid:1) BiophysicsandStructuralGenomicsDivision,SahaInstituteof
NuclearPhysics(HBNI),Kolkata,India
EWYMATHE´ (cid:1) TheOhioStateUniversityCollegeofMedicine,Columbus,OH,USA
MATTHEWMCKENZIE (cid:1) CentreforInnateImmunityandInfectiousDiseases,Hudson
InstituteofMedicalResearch,Clayton,VIC,Australia;DepartmentofMolecularand
TranslationalScience,MonashUniversity,Clayton,VIC,Australia;SchoolofLifeand
EnvironmentalSciences,DeakinUniversity,WaurnPonds,VIC,Australia
BEATAMICKIEWICZ (cid:1) DepartmentofBiologicalSciences,Bio-NMR-Centre,Universityof
Calgary,Calgary,AB,Canada
ELISAMORALES (cid:1) RobbinsCollegeofHealthandHumanSciences,BaylorUniversity,Waco,
TX,USA
ALICEC.NEWMAN (cid:1) WolfsonWohlCancerResearchCentre,InstituteofCancerSciences,
UniversityofGlasgow,Glasgow,UK
IOANNIS S.PATERAS (cid:1) MolecularCarcinogenesisGroup,DepartmentofHistologyand
Embryology,SchoolofMedicine,NationalandKapodistrianUniversityofAthens,Athens,
Greece
ANDYPATT (cid:1) TheOhioStateUniversityCollegeofMedicine,Columbus,OH,USA
AMANDAJ.PEARSON (cid:1) DepartmentofChemistryandBiochemistry,BaylorUniversity,Waco,
TX,USA
PAOLOE.PORPORATO (cid:1) DepartmentofMolecularBiotechnologyandHealthScience,
MolecularBiotechnologyCenter,UniversityofTorino,Torino,Italy
GUILLEMPRATX (cid:1) DivisionofMedicalPhysics,DepartmentofRadiationOncology,Stanford
University,Stanford,CA,USA
SHUOQIE (cid:1) DepartmentofBiology,CollegeofArtsandSciences,DrexelUniversity,
Philadelphia,PA,USA;DepartmentofBiochemistryandMolecularBiology,Medical
UniversityofSouthCarolina,Charleston,SC,USA
Contributors xi
LAKE-EEQUEK (cid:1) SchoolofMathematicsandStatistics,TheUniversityofSydney,Sydney,
NSW,Australia
JODIRATTNER (cid:1) ArnieCharbonneauCancerInstitute,UniversityofCalgary,Calgary,AB,
Canada
NIANLISANG (cid:1) DepartmentofBiology,CollegeofArtsandSciences,DrexelUniversity,
Philadelphia,PA,USA;SidneyKimmelCancerCenter,ThomasJeffersonUniversity,
Philadelphia,PA,USA
DEBANTISENGUPTA (cid:1) DivisionofMedicalPhysics,DepartmentofRadiationOncology,
StanfordUniversity,Stanford,CA,USA
MICHAELD.E.SEWELL (cid:1) ResearchDepartmentofCell&DevelopmentalBiology,University
CollegeLondon,London,UK
JALALSIDDOQUI (cid:1) TheOhioStateUniversityCollegeofMedicine,Columbus,OH,USA
SIMONESIDOLI (cid:1) DepartmentofBiochemistryandBiophysics,PerelmanSchoolofMedicine,
EpigeneticsInstitute,UniversityofPennsylvania,Philadelphia,PA,USA
GYORGY SZABADKAI (cid:1) DepartmentofCell&DevelopmentalBiology,UniversityCollege
London,London,UK;ConsortiumforMitochondrialResearch,UniversityCollegeLondon,
London,UK;TheFrancisCrickInstitute,London,UK;DepartmentofBiomedical
Sciences,UniversityofPadua,Padua,Italy
SOPHIE TREFELY (cid:1) DepartmentofCancerBiology,AbramsonFamilyCancerResearch
Institute,UniversityofPennsylvania,Philadelphia,PA,USA;A.J.DrexelAutism
Institute,DrexelUniversity,Philadelphia,PA,USA
AKIPUI-WAHTSE (cid:1) DepartmentofPathology,QueenMaryHospital,TheUniversityofHong
Kong,Pokfulam,HongKong
NIGELTURNER (cid:1) DepartmentofPharmacology,SchoolofMedicalSciences,UNSWAustralia,
Sydney,NSW,Australia
HANSJ.VOGEL (cid:1) DepartmentofBiologicalSciences,Bio-NMR-Centre,Universityof
Calgary,Calgary,AB,Canada
NATALIAVONMUHLINEN (cid:1) LaboratoryofHumanCarcinogenesis,NationalCancerInstitute,
NationalInstitutesofHealth,Bethesda,MD,USA
KARENH.VOUSDEN (cid:1) TheFrancisCrickInstitute,London,UK
TIMOTHYH.WITNEY (cid:1) ImagingChemistryandBiology,King’sCollegeLondon,London,UK
CARMENCHAK-LUIWONG (cid:1) DepartmentofPathology,QueenMaryHospital,TheUniversity
ofHongKong,Pokfulam,HongKong
ELISABETHWYART (cid:1) DepartmentofMolecularBiotechnologyandHealthScience,Molecular
BiotechnologyCenter,UniversityofTorino,Torino,Italy
BOFEI ZHANG (cid:1) TheOhioStateUniversityCollegeofMedicine,Columbus,OH,USA
JINGZHANG (cid:1) DepartmentofPathologyandLaboratoryMedicine,LinebergerComprehensive
CancerCenter,UNC-ChapelHill,ChapelHill,NC,USA
MISTYSHUOZHANG (cid:1) DepartmentofPathology,QueenMaryHospital,TheUniversityof
HongKong,Pokfulam,HongKong
QINGZHANG (cid:1) DepartmentofPathologyandLaboratoryMedicine,Lineberger
ComprehensiveCancerCenter,UNC-ChapelHill,ChapelHill,NC,USA;Departmentof
Pharmacology,UNC-ChapelHill,ChapelHill,NC,USA
TONGZHANG (cid:1) WolfsonWohlCancerResearchCentre,InstituteofCancerSciences,
UniversityofGlasgow,GarscubeEstate,Glasgow,UK