title: Stem Cell Factor-Based Identification and Functional Properties of In Vitro-Selected Subpopulations of Malignant Mesothelioma Cells.
abstract: 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.
authors.affiliation: Unit of Anatomy, Department of Medicine, University of Fribourg, Route Albert-Gockel 1, 1700 Fribourg, Switzerland. Electronic address: walter-vincent.blum@unifr.ch.
authors.forename: Walter
authors.initials: W
authors.lastname: Blum
authors.affiliation: Unit of Anatomy, Department of Medicine, University of Fribourg, Route Albert-Gockel 1, 1700 Fribourg, Switzerland.
authors.forename: László
authors.initials: L
authors.lastname: Pecze
authors.affiliation: Laboratory of Molecular Oncology, Lungen- und Thoraxonkologie Zentrum, University Hospital Zürich, Sternwartstrasse 14, 8091 Zürich, Switzerland.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Felley-Bosco
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON M5G 2C4, Canada.
authors.forename: Licun
authors.initials: L
authors.lastname: Wu
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON M5G 2C4, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: de Perrot
authors.affiliation: Unit of Anatomy, Department of Medicine, University of Fribourg, Route Albert-Gockel 1, 1700 Fribourg, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Schwaller
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D064032:Calbindin 2 / Q000032:analysis; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008654:Mesothelioma / Q000188:drug therapy / Q000473:pathology*; D000086002:Mesothelioma, Malignant; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D025581:Neurofibromin 2 / Q000032:analysis; D050814:Octamer Transcription Factor-3 / Q000032:analysis; D055748:SOXB1 Transcription Factors / Q000032:analysis; D019089:Stem Cell Factor / Q000032:analysis*
chemical_list: D000970:Antineoplastic Agents; D064032:Calbindin 2; D025581:Neurofibromin 2; D050814:Octamer Transcription Factor-3; D055748:SOXB1 Transcription Factors; D019089:Stem Cell Factor; D002945:Cisplatin
keywords: NF2; OCT4; SOX2; calretinin; cancer stem cells; defactinib; merlin; mesothelioma