D-dopachrome tautomerase is over-expressed in pancreatic ductal adenocarcinoma and acts cooperatively with macrophage migration inhibitory factor to promote cancer growth

2016 ◽  
Vol 139 (9) ◽  
pp. 2056-2067 ◽  
Author(s):  
Dawei Guo ◽  
Jinshuai Guo ◽  
Junchao Yao ◽  
Kun Jiang ◽  
Jianhua Hu ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Ductal Adenocarcinoma ◽  
Cancer Growth ◽  
Macrophage Migration ◽  
Dopachrome Tautomerase

scholarly journals Overexpression of Macrophage Migration Inhibitory Factor and Its Homologue D-Dopachrome Tautomerase as Negative Prognostic Factor in Neuroblastoma

2019 ◽  
Vol 9 (10) ◽  
pp. 284 ◽  
Author(s):  
Eugenio Cavalli ◽  
Emanuela Mazzon ◽  
Santa Mammana ◽  
Maria Basile ◽  
Salvo Lombardo ◽  
...  
Keyword(s):  
T Cells ◽  
Migration Inhibitory Factor ◽  
Macrophage Migration Inhibitory Factor ◽  
Cytotoxic T Cells ◽  
Hdac Inhibitors ◽  
Inhibitory Factor ◽  
Mycn Amplification ◽  
Macrophage Migration ◽  
Dopachrome Tautomerase

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.

scholarly journals Macrophage Migration Inhibitory Factor (MIF) and Its Homologue D-Dopachrome Tautomerase (DDT) Inversely Correlate with Inflammation in Discoid Lupus Erythematosus

Molecules ◽  
2021 ◽  
Vol 26 (1) ◽  
pp. 184
Author(s):  
Rosario Caltabiano ◽  
Rocco De Pasquale ◽  
Eliana Piombino ◽  
Giorgia Campo ◽  
Ferdinando Nicoletti ◽  
...  
Keyword(s):  
Migration Inhibitory Factor ◽  
Lupus Erythematosus ◽  
Macrophage Migration Inhibitory Factor ◽  
Normal Skin ◽  
Inhibitory Factor ◽  
Unknown Etiology ◽  
Discoid Lupus Erythematosus ◽  
Macrophage Migration ◽  
Dopachrome Tautomerase ◽  
Eccrine Glands

Discoid Lupus Erythematosus (DLE) is a chronic cutaneous disease of unknown etiology and of immunoinflammatory origin that is characterized by inflammatory plaques and may lead to disfiguring scarring and skin atrophy. Current treatments are limited, with a large proportion of patients either poorly or not responsive, which makes DLE an unmet medical need. Macrophage migration inhibitory factor (MIF) is the prototype of a pleiotropic family of cytokine that also includes the recently discovered homologue D-dopachrome tautomerase (DDT) or MIF2. MIF and DDT/MIF-2 exert several biological properties, primarily, but not exclusively of a proinflammatory nature. MIF and DDT have been suggested to play a key role in the pathogenesis of several autoimmune diseases, such as multiple sclerosis and type 1 diabetes, as well as in the development and progression of certain forms of cancers. In the present study, we have performed an immunohistochemistry analysis for the evaluation of MIF in DLE lesions and normal skin. We found high levels of MIF in the basal layer of the epidermis as well as in the cutaneous appendage (eccrine glands and sebocytes) of normal skin. In DLE lesions, we observed a significant negative correlation between the expression of MIF and the severity of inflammation. In addition, we performed an analysis of MIF and DDT expression levels in the skin of DLE patients in a publicly available microarray dataset. Interestingly, while these in silico data only evidenced a trend toward reduced levels of MIF, they demonstrated a significant pattern of expression and correlation of DDT with inflammatory infiltrates in DLE skins. Overall, our data support a protective role for endogenous MIF and possibly DDT in the regulation of homeostasis and inflammation in the skin and open up novel avenues for the treatment of DLE.

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