title: A Subset of Malignant Mesothelioma Tumors Retain Osteogenic Potential.
abstract: Malignant mesothelioma (MM) is an aggressive serosal tumor associated with asbestos exposure. We previously demonstrated that mesothelial cells differentiate into cells of different mesenchymal lineages and hypothesize that osseous tissue observed in a subset of MM patients is due to local differentiation of MM cells. In this study, the capacity of human and mouse MM cells to differentiate into osteoblast-like cells was determined in vitro using a functional model of bone nodule formation and in vivo using an established model of MM. Human and murine MM cell lines cultured in osteogenic medium expressed alkaline phosphatase and formed mineralized bone-like nodules. Several human and mouse MM cell lines also expressed a number of osteoblast phenotype markers, including runt-related transcription factor 2 (RUNX2), osteopontin, osteonectin and bone sialoprotein mRNA and protein. Histological analysis of murine MM tumors identified areas of ossification within the tumor, similar to those observed in human MM biopsies. These data demonstrate the ability of MM to differentiate into another mesenchymal cell type and suggest that MM cells may contribute to the formation of the heterologous elements observed in MM tumors.
authors.affiliation: Institute for Respiratory Health and Centre for Respiratory Health, School of Medicine and Pharmacology, University of Western Australia, Harry Perkins Institute of Medical Research, Nedlands, WA, Australia.
authors.forename: S M
authors.initials: SM
authors.lastname: Lansley
authors.affiliation: Institute for Respiratory Health and Centre for Respiratory Health, School of Medicine and Pharmacology, University of Western Australia, Harry Perkins Institute of Medical Research, Nedlands, WA, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Pedersen
authors.affiliation: National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia.|Harry Perkins Institute of Medical Research, Nedlands, WA, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Robinson
authors.affiliation: Institute for Respiratory Health and Centre for Respiratory Health, School of Medicine and Pharmacology, University of Western Australia, Harry Perkins Institute of Medical Research, Nedlands, WA, Australia.
authors.forename: R G
authors.initials: RG
authors.lastname: Searles
authors.affiliation: Anatomical Pathology Research, PathWest Laboratory Medicine WA and School of Pathology, University of Western Australia, Nedlands, WA, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Sterrett
authors.affiliation: National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia.|Harry Perkins Institute of Medical Research, Nedlands, WA, Australia.
authors.forename: I
authors.initials: I
authors.lastname: van Bruggen
authors.affiliation: National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia.|Harry Perkins Institute of Medical Research, Nedlands, WA, Australia.
authors.forename: R A
authors.initials: RA
authors.lastname: Lake
authors.affiliation: Institute for Respiratory Health and Centre for Respiratory Health, School of Medicine and Pharmacology, University of Western Australia, Harry Perkins Institute of Medical Research, Nedlands, WA, Australia.|Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia and Harry Perkins Institute of Medical Research, Nedlands, WA, Australia.
authors.forename: S E
authors.initials: SE
authors.lastname: Mutsaers
authors.affiliation: Institute for Respiratory Health and Centre for Respiratory Health, School of Medicine and Pharmacology, University of Western Australia, Harry Perkins Institute of Medical Research, Nedlands, WA, Australia.|Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia and Harry Perkins Institute of Medical Research, Nedlands, WA, Australia.
authors.forename: C M
authors.initials: CM
authors.lastname: Prêle
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D058574:Integrin-Binding Sialoprotein / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008654:Mesothelioma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000086002:Mesothelioma, Malignant; D051379:Mice; D009368:Neoplasm Transplantation; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D015676:Osteonectin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D050659:Core Binding Factor Alpha 1 Subunit; D058574:Integrin-Binding Sialoprotein; D015676:Osteonectin; D003907:Dexamethasone; D000469:Alkaline Phosphatase