103.30.11Cancer Biology2Outline1.How do cancer cells differ from normal cells?2.Tumor progression3.Molecular basis for cancerCancer is the second leading cause of death in the U.S.Cancer)accounts)for)nearly)one1quarter)of)deaths)in)the)United)States,)exceeded)only)by)heart)diseases.))In)2004,)there)were)553,888)cancer)deaths)in)the)US.Epithelial)cells:)carcinomas)))))80190%ConnecIve)Issues:)sarcomas)))1%Blood)and)lymphaIc)systems:)leukemias,)lymphomas)Neuronal)system:)neuroblastoma,)reInoblastoma,)etc.Epithelial)cellsConnecIve)IssueMuscle)IssueCancer may be derived from many tissuesThe)most)common)types)of)cancer)involve)epithelial)cells.)These)compose)80190%)of)cancers.A)cancer)like)this)would)be)called)Carcinoma.There)are)also)cancer)that)evolve)from)transformaIon)of)non1epithelial)cells.)There)are)three)main)groups:Cancer)of)the)connecIve)Issues:)Sarcoma+(1%)Cancer)of)the)blood)and)lymphaIc)system:)Leukemia,+Lymphoma,+MyelomaCancer)of)the)neuroectodermal)system)system:)Neuroblastoma,+Re?noblastomaCells within a tissue are normally highly organized and tightly regulatede.g.)intesIne e.g.)skinCancer cells exhibit behaviors found in normal cells during development differentiation, and homeostasisCancer: an aberration of normal developmentCancer+cells+exhibit+behaviors+found+in+normal+cells+during+development+&+differen?a?on.However,+in+cancer+cells+these+proper?es+are+separate d+f r om +nor m al+de ve lopmental+controls&+combined+in+unique+&+troublesome+ways.Cancer: an aberration of normal developmentCancer cells exhibit behaviors found in normal cells during development differentiation, and homeostasisHowever, cancer cells put together suitesOf cell behaviors in problematic waysAnd do so out of normal regulatory controlsCancer+cells+exhibit+behaviors+found+in+normal+cells+during+development+&+differen?a?on.However,+in+cancer+cells+these+proper?es+are+separate d+f r om +nor m al+de ve lopmental+controls&+combined+in+unique+&+troublesome+ways.Most normal cells have a limited potential to dividesenescent)cellsProperties of Cancer CellsIn)what)ways)cancer)cells)differ)from)normal)cells?1.)Cancer)cells)are)"immortalized"1)i.e.)conInue)to)divide)indefinitelywithout)differenIaIng1)a)normal)property)of)body's)stem)cellsNormal stem cells can divide indefinitely, but under tight controlSelfJrenewing+stem+cellDifferen?ated+cellsIn)what)ways)cancer)cells)differ)from)normal)cells?1.)Cancer)cells)are)"immortalized"1)i.e.)conInue)to)divide)indefinitelywithout)differenIaIng1)a)normal)property)of)body's)stem)cellsCancer cells are "immortalized”,just like stem cells, but w/o controlProperties of Cancer CellsSelfJrenewing+stem+cellDifferen?ated+cellsCancer+cellIn)what)ways)cancer)cells)differ)from)normal)cells?1.)Cancer)cells)are)"immortalized"1)i.e.)conInue)to)divide)indefinitelywithout)differenIaIng1)a)normal)property)of)body's)stem)cellsMost Normal cells differentiate3.)Cancer)cells)fail)to)form)differenIated)Issues)like)epidermal)sheets,)or)specific)blood)cells)))But stem cells do NOTdifferentiate3.)Cancer)cells)fail)to)form)differenIated)Issues)like)epidermal)sheets,)or)specific)blood)cells)))Like normal stem cells cancer cells do not differentiatetumor3.)Cancer)cells)fail)to)form)differenIated)Issues)like)epidermal)sheets.)))Figure)20129)!Molecular!Biology!of!the!Cell)(©)Garland)Science)2008)Most normal cells stop proliferating under contact inhibitionin!vitroin!vivo2.)Cancer)cells)not)under)contact)inhibiIonNormal)cells)stop)dividing)when)come)into)contact)with)neighbors.))Normal)blastocyst)stage)embryonic)cells)share)this)property.Figure)20129)!Molecular!Biology!of!the!Cell)(©)Garland)Science)2008)Cancer cells do not exhibit contact inhibition2.)Cancer)cells)not)under)contact)inhibiIonHowever cells of early embryosalso lack contact inhibition - thus cancer cells exhibit properties off embryonic cellsNormal “Transformed”Cancer cells exhibit altered cell adhesion and cytoskeletal organizationThese changes in cell shape and behavior are shared by many migrating cells,including those that migrate into wound sitesLate stage cancer cells are invasiveFigure)20117)!Molecular!Biology!of!the!Cell)(©)Garland)Science)2008)normal+?ssueinvasive+tumor5.)Cancer)cells)are)invasiveNormal cells can be invasive at the right time and place5.)Normal)cells)can)also)be)invasive)(inflammatory)response,)EMT).A)neutrophil)penetrates)through)blood)vessels)and)the)extra1cellular)matrix)as)part)of)an)inflammatory)responseNormal cells that are starved for O2 Induce AngiogenesisConsequences 1. Nutrients and oxygen are supplied to the tissueCan’t breathe!Send Blood vesselsCancer Cells also Induce AngiogenesisConsequences 1. Nutrients and oxygen are supplied to the tumor2. New blood vessels provide as easy way outNormal cells may undergo apoptosisAs part of a developmental programwhen cells become “dangerous” (e.g. DNA damage)4.)Cancer)cells)do)not)undergo)normal)programmed)cell+death.Properties of Cancer CellsCancer cells escape apoptosisBlue+cells+=+breast+cancer+cellsYellow+cells+=+apopto?c+cellsDave!McCarthy!and!Annie!Cavanagh4.)Cancer)cells)do)not)undergo)normal)programmed)cell+death.Properties of Cancer Cells• Immortalized• Do not differentiate• Fail to exhibit contact inhibition• Invasive• Escape apoptosisFigure 20-9 Molecular Biology of the Cell (© Garland Science 2008)Cancer develops through gradual changes in cell morphology and propertiesTumor)progression,)from)over1proliferaIon,)to)–”taking)over”)the)Issue)and)eventually1)invasion)through)the)basal)laminaTumor ProgressionTumor = abnormal growth of solid tissueBenign- self containedMalignant-
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