肿瘤的细胞微环境和肿瘤转移

复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterBasicClinicalOncologyTheCellularMicroenviromentandMetastasesFudanUniversityCancerCenterProf.Dr.WentaoYANG复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterOriginandHistory•TheoldestandoneofthemostprestigiouscancercentersinChina•Foundedin1931asSino-BelgiumRadiumInstitutebyKingdomofBelgium•FormerlyaffiliatedtoShanghaiMedicalUniversity(1954-2000)复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterSino-BelgiumRadiumInstitutein1950复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterToday•1205-bedCancerCenter•Outpatients/year:932,000•Inpatients/year:40600•Operation/year:23219•Numberofemployees:1300•AffiliatedtoFudanUniversitysince2000复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterBasicClinicOncologyCourseObjectives:•Toknowtheetiologyandbiologyofcancerandthesituationofcancerprevention.•Tolearnthebasicsofcancerdiagnosis,includingtheclinical,imaging,pathologyandthelabs•Toknowtheprinciplesofcancertherapy,especiallythemultidisciplinarymodalitiesforacomprehensivecancerpatientcare•Toknowthefrontiersofbasicandclinicalresearchesbriefly复旦大学上海医学院肿瘤学系FudanUniversityCancerCenter复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterDefinitionofMetastasisTheprocesswherebymalignanttumorsspreadfromtheirsiteoforigin(theprimarytumor)toformtumorsatsecondarysites(secondarytumor).Acquisitionofthecapabilityforinvasionandmetastasisisthehallmarksofcancer.Metastasisremainsthemajordriverofmortalityinpatientswithcancer.复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterBoneMetastasisLungMetastasis复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterBrainMetastasis复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterSofttissuesarcomainleftleg复旦大学上海医学院肿瘤学系FudanUniversityCancerCenteralveolarsoftpartsarcomainleftleg复旦大学上海医学院肿瘤学系FudanUniversityCancerCenter复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterLungalveolarsoftpartsarcoma复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterMalignantPhyllodesTumoroftheBreast复旦大学上海医学院肿瘤学系FudanUniversityCancerCenter复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterMalignantPhyllodesTumormetastasizetothelung复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterMetastaticcarcinomaoftheovaryfromthestomach复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterClassicTypeTubularTypeSclerosingTypeClassicType复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterPulmonaryblastomametastasizetorightovary复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterMetastaticcarcinomaoftheovaryfromthecolonFromBlaustein’sPathologyoftheFemaleGenitalTract复旦大学上海医学院肿瘤学系FudanUniversityCancerCenter复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterMetastaticcarcinomaoftheovaryfromtheappendix复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterTheessentialcomponentinprovidingqualitycancercareThestagingofcancersisbasedonthesizeoftheprimarylesion,itsextentofspreadtoregionallymphnodes,andmetastases.Widelyusedisaso-calledTNMsystem.复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterT:PrimaryTumorT1,T2,T3,orT4,withincreasingsizeofprimarylesionN:regionallymphnodeinvolvementNo,N1,N2,N3toindicateprogressivelyadvancingnodaldiseaseM:metastasesMoorM,accordingtowhethertherearedistantmetastases.复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterMetastaticcancerisresponsibleforabout90%ofcancermortality.-understandinghowcellsdisseminatefromtheprimarytumortoinvadeandsuccessfullycolonizedistanttissuesrepresentstheLEASTunderstoodandthemostdeadlyareaofcancerbiology.复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterMultistepProcessofMetastasisMetastasisisinfluencedbytheinteractionsbetweenTumorcellsandhostcellsImmediateandextendedtumormicroenviromentsMandiMurph,ResearchonMelanoma复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterMultistepprocessedaccomplishedbymetastasizingcancerMotilityandtissueinvasionIntravasation(Alternatively,canenterlymphaticvessels)Survivalinthebloodstream(trauma,immunecells,oxygenlevels,growthfactoravailabilityetc.)ArrestatnewlocationExtravasationAttraction/inductionofnewstromalcells(mayoccurBEFOREmetastasisoccurs).GrowthandProliferation….Angiogenesis复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterFigure14.4TheBiologyofCancer(©GarlandScience2007)p.591Tumormetastasisisacomplex,multistepprocessconsistingofaseriesofdiscretebiologicalprocesses.复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterInvasionandMetastasis•cancercellsproliferateandspread(metastasize)tootherpartsofthebody•Invasion-directmigrationandpenetrationintoneighboringtissues•Metastasis-cancercellspenetrateintolymphaticsystemandbloodvessels复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterAcquiringInvasivenessPrimarycarcinomacell(s)must:•Disengagefromtheirneighboringepithelialcells•Becomemotile•Degradethesurroundingextracellularmatrix复旦大学上海医学院肿瘤学系FudanUniversityCancerCenterInvasionandCellMotility•Thefirststepofmetastasis.•Normaltissuerequiresproperadhesionswithbasementmembraneand/orneighboringcells.•Cellsmustundergochangesintheircell-cellandcell-matrixadhesioninteractionstodissociatethemselvesfromthetumor.•Tumorcellsdisplaydiminishedcellularadhesion,allowingthemtobecomemotile.•Tumorcellsusetheirmigratoryandinvasivepropertiesinordertoburrowthroughsurroundingextracellularstromaandtogainentryintobloodvesselsandlymphatics.•Cellmotilityisacriticalcomponentoftheinvasivephenotype.复旦大学上海医学院肿瘤