Stem cell factor-based identification and functional properties of in vitro-selected subpopulations of malignant mesothelioma cells
- Blum, Walter Unit of Anatomy, Department of Medicine, University of Fribourg, Switzerland
- Pecze, László Unit of Anatomy, Department of Medicine, University of Fribourg, Switzerland
- Felley-Bosco, Emanuela Laboratory of Molecular Oncology, Lungen- und Thoraxonkologie Zentrum, University Hospital Zürich, Switzerland
- Wu, Licun Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Canada
- Perrot, Marc de Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Canada
- Schwaller, Beat Unit of Anatomy, Department of Medicine, University of Fribourg, Switzerland
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11.04.2017
Published in:
- Stem Cell Reports. - 2017, vol. 8, no. 4, p. 1005–1017
English
Malignant mesothelioma (MM) is an aggressive neoplasm characterized by a poor patient survival rate, because of rapid tumor recurrence following first-line therapy. Cancer stem cells (CSCs) are assumed to be responsible for initiating tumorigenesis and driving relapse after therapeutic interventions. CSC-enriched MM cell subpopulations were identified by an OCT4/SOX2 reporter approach and were characterized by (1) increased resistance to cisplatin, (2) increased sensitivity toward the FAK inhibitor VS-6063 in vitro, and (3) a higher tumor-initiating capacity in vivo in orthotopic xenograft and allograft mouse models. Overexpression of NF2 (neurofibromatosis 2, merlin), a tumor suppressor often mutated or lost in MM, did not affect proliferation and viability of CSC-enriched MM populations but robustly decreased the viability of reporter-negative cells. In contrast, downregulation of calretinin strongly decreased proliferation and viability of both populations. In summary, we have enriched and characterized a small MM cell subpopulation that bears the expected CSC characteristics.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Médecine
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 288979
- DOI 10.1016/j.stemcr.2017.02.005
- Persistent URL
- https://folia.unifr.ch/unifr/documents/305784
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