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

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

URL: https://www.ncbi.nlm.nih.gov/pubmed/30177776
DOI: 10.1038/s41556-018-0179-z

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
Depositing User: Matthew Dunn
Date: 3 September 2018
Date Deposited: 06 Sep 2018 18:40
Last Modified: 23 Apr 2019 14:40
PMCID: PMC6163039
Related URLs:
URI: http://repository.cshl.edu/id/eprint/37194

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