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.

Lenos, K.J., Miedema, D.M., Lodestijn, S.C., Nijman, L.E., van den Bosch, T., Romero Ros, X., et al. (2018). Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer. NATURE CELL BIOLOGY, 20, 1193-1202 [10.1038/s41556-018-0179-z].

Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer

Stassi, Giorgio;
2018-01-01

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.
2018
Lenos, K.J., Miedema, D.M., Lodestijn, S.C., Nijman, L.E., van den Bosch, T., Romero Ros, X., et al. (2018). Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer. NATURE CELL BIOLOGY, 20, 1193-1202 [10.1038/s41556-018-0179-z].
File in questo prodotto:
File Dimensione Formato  
10.1038@s41556-018-0179-z.pdf

Solo gestori archvio

Descrizione: head of print
Tipologia: Versione Editoriale
Dimensione 4.81 MB
Formato Adobe PDF
4.81 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
_stem-prima parte.pdf

Solo gestori archvio

Descrizione: 1. parte
Tipologia: Versione Editoriale
Dimensione 6.35 MB
Formato Adobe PDF
6.35 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
stem-seconda parte (1).pdf

Solo gestori archvio

Descrizione: 2. parte
Tipologia: Versione Editoriale
Dimensione 6.11 MB
Formato Adobe PDF
6.11 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/297178
Citazioni
  • ???jsp.display-item.citation.pmc??? 88
  • Scopus 132
  • ???jsp.display-item.citation.isi??? 124
social impact