Role of MIF/CD74 signaling pathway in the development of pleural mesothelioma

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 rece...

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Bibliographic Details
Published in:Oncotarget 2016-03, Vol.7 (10), p.11512-11525
Main Authors: D'Amato-Brito, Cintia, Cipriano, Davide, Colin, Didier J, Germain, Stéphane, Seimbille, Yann, Robert, John H, Triponez, Frédéric, Serre-Beinier, Véronique
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - genetics
Antigens, CD - metabolism
Cell Line, Tumor
Cell Proliferation - physiology
Female
Heterografts
Humans
Intramolecular Oxidoreductases - genetics
Intramolecular Oxidoreductases - metabolism
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Macrophage Migration-Inhibitory Factors - genetics
Macrophage Migration-Inhibitory Factors - metabolism
Mesothelioma - genetics
Mesothelioma - metabolism
Mesothelioma - pathology
Mesothelioma, Malignant
Mice
Mice, Nude
Pleural Neoplasms - genetics
Pleural Neoplasms - metabolism
Pleural Neoplasms - pathology
Research Paper
Sialyltransferases - genetics
Sialyltransferases - metabolism
Signal Transduction
Transfection
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.7314