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RESEARCH PRODUCT
Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer
Sophie C. LodestijnXavier Romero RosDouglas J. WintonFelipe De Sousa E MeloMaarten F. BijlsmaKristiaan J. LenosJan Paul MedemaNicolas LéveilléFilipe C. LourencoLianne KoensGuillaume HypoliteDaniël M. MiedemaMaartje Van Der HeijdenGiorgio StassiLisanne E. NijmanScott K. LyonsLouis VermeulenTom Van Den BoschJoy OttenPatrick VeermanRonja S. AdamAnita Van OortMaria C. LeccaEdward MorrisseySanne M. Van Neervensubject
0301 basic medicineColorectal cancerCellClone (cell biology)Mice NudeContext (language use)Colon cancer cancer stem cells tumor microenvironment.Article03 medical and health sciencesCancer stem cellCancer Stem CellsAntineoplastic Combined Chemotherapy ProtocolsmedicineTumor MicroenvironmentAnimalsHumansOsteopontin (OPN Spp1)OsteopontinStem Cell DynamicsCells CulturedCell ProliferationbiologyColon CancerGene Expression ProfilingCancerDisease RelapseTumour growthCell Biologymedicine.diseaseXenograft Model Antitumor AssaysCell biologyGene Expression Regulation NeoplasticOxaliplatinTamoxifen030104 developmental biologymedicine.anatomical_structureColonic Neoplasmsbiology.proteinNeoplastic Stem CellsTherapyStem cellCuesdescription
Solid malignancies have been speculated to depend on cancer stem cells (CSCs) for expansion and relapse after therapy. Here we report on quantitative analyses of lineage tracing data from primary colon cancer xenograft tissue to assess CSC functionality in a human solid malignancy. The temporally obtained clone size distribution data support a model in which stem cell function in established cancers is not intrinsically, but is entirely spatiotemporally orchestrated. Functional stem cells that drive tumour expansion predominantly reside at the tumour edge, close to cancer-associated fibroblasts. Hence, stem cell properties change in time depending on the cell location. Furthermore, although chemotherapy enriches for cells with a CSC phenotype, in this context functional stem cell properties are also fully defined by the microenvironment. To conclude, we identified osteopontin as a key cancer-associated fibroblast-produced factor that drives in situ clonogenicity in colon cancer.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-09-03 | Nature cell biology |