Role of MIF/CD74 signaling pathway in the development of pleural mesothelioma
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Cintia D’Amato-Brito1, Davide Cipriano1, Didier J. Colin2, Stéphane Germain2, Yann Seimbille3, John H. Robert1, Frédéric Triponez1, Véronique Serre-Beinier1
1Department of Thoracic and Endocrine Surgery, University Hospitals and University of Geneva, Geneva, Switzerland
2MicroPET/SPECT/CT Imaging Laboratory, Centre for BioMedical Imaging (CIBM), University Hospitals and University of Geneva, Geneva, Switzerland
3Cyclotron Unit, University Hospitals and University of Geneva, Geneva, Switzerland
Véronique Serre-Beinier, e-mail: Veronique.Serre-Beinier@hcuge.ch
Keywords: cancer, pleura, mesothelioma, macrophage migration inhibitory factor (MIF), CD74
Received: May 27, 2015 Accepted: January 26, 2016 Published: February 11, 2016
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.
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