title: Role of MIF/CD74 signaling pathway in the development of pleural mesothelioma.
abstract: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine implicated in acute and chronic inflammatory diseases. MIF is overexpressed in various tumors. It displays a number of functions that provide a direct link between the process of inflammation and tumor growth. Our group recently identified the MIF-receptor CD74 as an independent prognostic factor for overall survival in patients with malignant pleural mesothelioma.In the present study, we compared the levels of expression of MIF and CD74 in different human mesothelioma cell lines and investigated their physiopathological functions in vitro and in vivo.Human mesothelioma cells expressed more CD74 and secreted less MIF than non tumoral MeT5A cells, suggesting a higher sensitivity to MIF. In mesothelioma cells, high MIF levels were associated with a high multiplication rate of cells. In vitro, reduction of MIF or CD74 levels in both mesothelioma cell lines showed that the MIF/CD74 signaling pathway promoted tumor cell proliferation and protected MPM cells from apoptosis. Finally, mesothelioma cell lines expressing high CD74 levels had a low tumorigenic potential after xenogeneic implantation in athymic nude mice.All these data highlight the complexity of the MIF/CD74 signaling pathway in the development of mesothelioma.
authors.affiliation: Department of Thoracic and Endocrine Surgery, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Cintia
authors.initials: C
authors.lastname: D'Amato-Brito
authors.affiliation: Department of Thoracic and Endocrine Surgery, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Davide
authors.initials: D
authors.lastname: Cipriano
authors.affiliation: MicroPET/SPECT/CT Imaging Laboratory, Centre for BioMedical Imaging (CIBM), University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Didier J
authors.initials: DJ
authors.lastname: Colin
authors.affiliation: MicroPET/SPECT/CT Imaging Laboratory, Centre for BioMedical Imaging (CIBM), University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Germain
authors.affiliation: Cyclotron Unit, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Yann
authors.initials: Y
authors.lastname: Seimbille
authors.affiliation: Department of Thoracic and Endocrine Surgery, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: John H
authors.initials: JH
authors.lastname: Robert
authors.affiliation: Department of Thoracic and Endocrine Surgery, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Triponez
authors.affiliation: Department of Thoracic and Endocrine Surgery, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Véronique
authors.initials: V
authors.lastname: Serre-Beinier
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D064593:Heterografts; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D051379:Mice; D008819:Mice, Nude; D010997:Pleural Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D015703:Antigens, CD; D019746:Intramolecular Oxidoreductases; D008263:Macrophage Migration-Inhibitory Factors; D012799:Sialyltransferases; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase; C515598:MIF protein, human
keywords: CD74; cancer; macrophage migration inhibitory factor (MIF); mesothelioma; pleura