Overexpression of Macrophage Migration Inhibitory Factor and Its Homologue D-Dopachrome Tautomerase as Negative Prognostic Factor in Neuroblastoma
Neuroblastoma (NB) represents one of the most frequent pediatric solid tumors. Macrophage migration inhibitory factor (MIF) is a cytokine exerting multiple biological functions. More recently, a second member of the MIF family of cytokine has been identified, the D-dopachrome tautomerase (DDT), that...
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MDPI AG
2019-10-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/9/10/284 |
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| author | Eugenio Cavalli Emanuela Mazzon Santa Mammana Maria Sofia Basile Salvo Danilo Lombardo Katia Mangano Placido Bramanti Ferdinando Nicoletti Paolo Fagone Maria Cristina Petralia |
| author_facet | Eugenio Cavalli Emanuela Mazzon Santa Mammana Maria Sofia Basile Salvo Danilo Lombardo Katia Mangano Placido Bramanti Ferdinando Nicoletti Paolo Fagone Maria Cristina Petralia |
| author_sort | Eugenio Cavalli |
| collection | DOAJ |
| description | Neuroblastoma (NB) represents one of the most frequent pediatric solid tumors. Macrophage migration inhibitory factor (MIF) is a cytokine exerting multiple biological functions. More recently, a second member of the MIF family of cytokine has been identified, the D-dopachrome tautomerase (DDT), that exerts several overlapping functions with MIF. Growing evidence suggests a key role for MIF and DDT in the development of cancer. The aim of this study is to characterize the prognostic value of MIF and DDT in NB. We show that higher expression levels of MIF and DDT in Stage 4 NB samples are associated with a poorer prognosis, independently of the presence of MYCN amplification. Moreover, higher levels of MIF are mostly enriched by Th1 cells, while lower levels of MIF are associated with an increased proportion of B cells, Cytotoxic T cells, Dendritic cells and Natural Killer T cells. We also show that treatment with the histone deacetylase (HDAC) inhibitor, vorinostat, of the NB cell line, SH-SY5Y, determines a significant reduction in the expression of both MIF and DDT. Finally, MIF and DDT inhibition by short interfering RNA is able to revert vincristine sensitivity in vitro. Overall, our data suggest that MIF exert pro-tumorigenic properties in NB, likely by dampening antigen presentation and cytotoxic immune responses, and we propose the HDAC inhibitors as a potential therapeutic strategy for NB patients. |
| first_indexed | 2024-12-14T01:00:43Z |
| format | Article |
| id | doaj.art-06b87b976aab4e98b4694206233c8e61 |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-12-14T01:00:43Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-06b87b976aab4e98b4694206233c8e612022-12-21T23:23:16ZengMDPI AGBrain Sciences2076-34252019-10-0191028410.3390/brainsci9100284brainsci9100284Overexpression of Macrophage Migration Inhibitory Factor and Its Homologue D-Dopachrome Tautomerase as Negative Prognostic Factor in NeuroblastomaEugenio Cavalli0Emanuela Mazzon1Santa Mammana2Maria Sofia Basile3Salvo Danilo Lombardo4Katia Mangano5Placido Bramanti6Ferdinando Nicoletti7Paolo Fagone8Maria Cristina Petralia9IRCCS Centro Neurolesi Bonino Pulejo, C.da Casazza, 98124 Messina, ItalyIRCCS Centro Neurolesi Bonino Pulejo, C.da Casazza, 98124 Messina, ItalyIRCCS Centro Neurolesi Bonino Pulejo, C.da Casazza, 98124 Messina, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, ItalyIRCCS Centro Neurolesi Bonino Pulejo, C.da Casazza, 98124 Messina, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, ItalyIRCCS Centro Neurolesi Bonino Pulejo, C.da Casazza, 98124 Messina, ItalyNeuroblastoma (NB) represents one of the most frequent pediatric solid tumors. Macrophage migration inhibitory factor (MIF) is a cytokine exerting multiple biological functions. More recently, a second member of the MIF family of cytokine has been identified, the D-dopachrome tautomerase (DDT), that exerts several overlapping functions with MIF. Growing evidence suggests a key role for MIF and DDT in the development of cancer. The aim of this study is to characterize the prognostic value of MIF and DDT in NB. We show that higher expression levels of MIF and DDT in Stage 4 NB samples are associated with a poorer prognosis, independently of the presence of MYCN amplification. Moreover, higher levels of MIF are mostly enriched by Th1 cells, while lower levels of MIF are associated with an increased proportion of B cells, Cytotoxic T cells, Dendritic cells and Natural Killer T cells. We also show that treatment with the histone deacetylase (HDAC) inhibitor, vorinostat, of the NB cell line, SH-SY5Y, determines a significant reduction in the expression of both MIF and DDT. Finally, MIF and DDT inhibition by short interfering RNA is able to revert vincristine sensitivity in vitro. Overall, our data suggest that MIF exert pro-tumorigenic properties in NB, likely by dampening antigen presentation and cytotoxic immune responses, and we propose the HDAC inhibitors as a potential therapeutic strategy for NB patients.https://www.mdpi.com/2076-3425/9/10/284neuroblastomamifddt |
| spellingShingle | Eugenio Cavalli Emanuela Mazzon Santa Mammana Maria Sofia Basile Salvo Danilo Lombardo Katia Mangano Placido Bramanti Ferdinando Nicoletti Paolo Fagone Maria Cristina Petralia Overexpression of Macrophage Migration Inhibitory Factor and Its Homologue D-Dopachrome Tautomerase as Negative Prognostic Factor in Neuroblastoma Brain Sciences neuroblastoma mif ddt |
| title | Overexpression of Macrophage Migration Inhibitory Factor and Its Homologue D-Dopachrome Tautomerase as Negative Prognostic Factor in Neuroblastoma |
| title_full | Overexpression of Macrophage Migration Inhibitory Factor and Its Homologue D-Dopachrome Tautomerase as Negative Prognostic Factor in Neuroblastoma |
| title_fullStr | Overexpression of Macrophage Migration Inhibitory Factor and Its Homologue D-Dopachrome Tautomerase as Negative Prognostic Factor in Neuroblastoma |
| title_full_unstemmed | Overexpression of Macrophage Migration Inhibitory Factor and Its Homologue D-Dopachrome Tautomerase as Negative Prognostic Factor in Neuroblastoma |
| title_short | Overexpression of Macrophage Migration Inhibitory Factor and Its Homologue D-Dopachrome Tautomerase as Negative Prognostic Factor in Neuroblastoma |
| title_sort | overexpression of macrophage migration inhibitory factor and its homologue d dopachrome tautomerase as negative prognostic factor in neuroblastoma |
| topic | neuroblastoma mif ddt |
| url | https://www.mdpi.com/2076-3425/9/10/284 |
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