Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer
| Autor: | Sophie C. Lodestijn, Xavier Romero Ros, Douglas J. Winton, Felipe De Sousa E Melo, Maarten F. Bijlsma, Kristiaan J. Lenos, Jan Paul Medema, Nicolas Léveillé, Filipe C. Lourenco, Lianne Koens, Guillaume Hypolite, Daniël M. Miedema, Maartje van der Heijden, Giorgio Stassi, Lisanne E. Nijman, Scott K. Lyons, Louis Vermeulen, Tom van den Bosch, Joy Otten, Patrick Veerman, Ronja S. Adam, Anita van Oort, Maria C. Lecca, Edward Morrissey, Sanne M. van Neerven |
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| Přispěvatelé: | Lenos, Kristiaan J, Miedema, Daniël M, Lodestijn, Sophie C, Nijman, Lisanne E, van den Bosch, Tom, Romero Ros, Xavier, Lourenço, Filipe C, Lecca, Maria C, van der Heijden, Maartje, van Neerven, Sanne M, van Oort, Anita, Leveille, Nicola, Adam, Ronja S, de Sousa E Melo, Felipe, Otten, Joy, Veerman, Patrick, Hypolite, Guillaume, Koens, Lianne, Lyons, Scott K, Stassi, Giorgio, Winton, Douglas J, Medema, Jan Paul, Morrissey, Edward, Bijlsma, Maarten F, Vermeulen, Louis, Center of Experimental and Molecular Medicine, CCA - Cancer biology and immunology, Graduate School, AGEM - Re-generation and cancer of the digestive system, AGEM - Digestive immunity, Pathology, Radiotherapy |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Colorectal cancer Cell Clone (cell biology) Mice Nude Context (language use) Colon cancer cancer stem cells tumor microenvironment Article 03 medical and health sciences Cancer stem cell Cancer Stem Cells Antineoplastic Combined Chemotherapy Protocols medicine Tumor Microenvironment Animals Humans Osteopontin (OPN Spp1) Osteopontin Stem Cell Dynamics Cells Cultured Cell Proliferation biology Colon Cancer Gene Expression Profiling Cancer Disease Relapse Tumour growth Cell Biology medicine.disease Xenograft Model Antitumor Assays Cell biology Gene Expression Regulation Neoplastic Oxaliplatin Tamoxifen 030104 developmental biology medicine.anatomical_structure Colonic Neoplasms biology.protein Neoplastic Stem Cells Therapy Stem cell Cues |
| Zdroj: | Nature cell biology Nature cell biology, 20(10), 1193-1202. Nature Publishing Group Nature Cell Biology |
| ISSN: | 1476-4679 1465-7392 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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