Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer
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 ob...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Nature Research
2018
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| _version_ | 1797103965341483008 |
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| author | Lenos, K Miedema, D Lodestijn, S Nijman, L Van Den Bosch, T Romero Ros, X Lourenço, F Lecca, M Van Der Heijden, M Van Neerven, S Van Oort, A Leveille, N Adam, R De Sousa E Melo, F Otten, J Veerman, P Hypolite, G Koens, L Lyons, S Stassi, G Winton, D Medema, J Morrissey, E Bijlsma, M Vermeulen, L |
| author_facet | Lenos, K Miedema, D Lodestijn, S Nijman, L Van Den Bosch, T Romero Ros, X Lourenço, F Lecca, M Van Der Heijden, M Van Neerven, S Van Oort, A Leveille, N Adam, R De Sousa E Melo, F Otten, J Veerman, P Hypolite, G Koens, L Lyons, S Stassi, G Winton, D Medema, J Morrissey, E Bijlsma, M Vermeulen, L |
| author_sort | Lenos, K |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T06:27:33Z |
| format | Journal article |
| id | oxford-uuid:f4d423dd-18f0-4f13-ac74-cdaa6d61d464 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:27:33Z |
| publishDate | 2018 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:f4d423dd-18f0-4f13-ac74-cdaa6d61d4642022-03-27T12:22:51ZStem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancerJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f4d423dd-18f0-4f13-ac74-cdaa6d61d464EnglishSymplectic Elements at OxfordNature Research2018Lenos, KMiedema, DLodestijn, SNijman, LVan Den Bosch, TRomero Ros, XLourenço, FLecca, MVan Der Heijden, MVan Neerven, SVan Oort, ALeveille, NAdam, RDe Sousa E Melo, FOtten, JVeerman, PHypolite, GKoens, LLyons, SStassi, GWinton, DMedema, JMorrissey, EBijlsma, MVermeulen, LSolid 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. |
| spellingShingle | Lenos, K Miedema, D Lodestijn, S Nijman, L Van Den Bosch, T Romero Ros, X Lourenço, F Lecca, M Van Der Heijden, M Van Neerven, S Van Oort, A Leveille, N Adam, R De Sousa E Melo, F Otten, J Veerman, P Hypolite, G Koens, L Lyons, S Stassi, G Winton, D Medema, J Morrissey, E Bijlsma, M Vermeulen, L Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer |
| title | Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer |
| title_full | Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer |
| title_fullStr | Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer |
| title_full_unstemmed | Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer |
| title_short | Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer |
| title_sort | stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer |
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