Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer.
Nat Cell Biol
; 20(10): 1193-1202, 2018 10.
Article
en En
| MEDLINE
| ID: mdl-30177776
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Madre Neoplásicas
/
Protocolos de Quimioterapia Combinada Antineoplásica
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Neoplasias del Colon
/
Ensayos Antitumor por Modelo de Xenoinjerto
/
Proliferación Celular
/
Microambiente Tumoral
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Cell Biol
Año:
2018
Tipo del documento:
Article
País de afiliación:
Países Bajos