Lenos, K. J., Miedema, D. M., Lodestijn, S. C., Nijman, L. E., van den Bosch, T., Romero Ros, X., Lourenco, F. C., Lecca, M. C., van der Heijden, M., van Neerven, S. M., van Oort, A., Leveille, N., Adam, R. S., de Sousa, E. Melo F., Otten, J., Veerman, P., Hypolite, G., Koens, L., Lyons, S. K., Stassi, G., Winton, D. J., Medema, J. P., Morrissey, E., Bijlsma, M. F., Vermeulen, L. (September 2018) Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer. Nat Cell Biol, 20 (10). pp. 1193-1202. ISSN 1465-7392
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.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cancer > cancer types > colon cancer diseases & disorders > cancer > cancer types > colon cancer organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells |
| CSHL Authors: | |
| Communities: | CSHL labs > Lyons lab CSHL Cancer Center Program > Cellular Communication in Cancer Program |
| Depositing User: | Matthew Dunn |
| Date: | 3 September 2018 |
| Date Deposited: | 06 Sep 2018 18:40 |
| Last Modified: | 26 Oct 2020 15:57 |
| PMCID: | PMC6163039 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/37194 |
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