Intracellular distribution of macrophage migration inhibitory factor predicts the prognosis of patients with adenocarcinoma of the lung

Kamimura, Akiko; Kamachi, Masafumi; Nishihira, Jun; Ogura, Shinji; Isobe, Hiroshi; Dosaka‐Akita, Hirotoshi; Ogata, Akihiko; Shindoh, Masanobu; Ohbuchi, Toshiro; Kawakami, Yoshikazu

doi:10.1002/1097-0142(20000715)89:2<334::aid-cncr18>3.0.co;2-n

Cited by 136 publications

(69 citation statements)

References 30 publications

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“…Of particular note is that NcMIF was clearly present in the nuclei. There were reports describing the localization of MIF in nuclei (Kamimura et al, 2000; Vedder et al, 2000), but these observations were not reported in later studies. NcMIF, as shown in the present study, as well as MIFs from other species does not contain a signal sequence or a nuclear localization signal (Arnoys and Wang, 2007), but the localization in the cytoplasm and nucleic as well as the extracellular compartments was apparent (Vedder et al, 2000).…”

Section: Discussionmentioning

confidence: 92%

Characterization of Neospora caninum macrophage migration inhibitory factor

Qu¹,

Fetterer²,

Jenkins³

et al. 2013

Experimental Parasitology

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The present study is the first characterization of Neospora caninum macrophage migration inhibitory factor (NcMIF). BLAST-N analysis of NcMIF revealed high similarity (87%) to the Toxoplasma gondii MIF. NcMIF was cloned and expressed in Escherichia coli in 3 forms, NcMIF (mature protein), NcMIFm (mutation of proline -2 to glycine), and NcMIFhis (addition of a polyhistidine tag at the N-terminus). None of these recombinant NcMIFs (rNcMIF) had tautomerase, oxidoreductase, or immunologic regulatory activities. rNcMIF was unable to compete with recombinant human MIF for a MIF receptor (CD74), suggesting that NcMIF does not bind to this MIF receptor. The glycine substitution for proline-2 of NcMIF resulted in increased retention time on SEC-HPLC and decreased formation of dimers and trimers. The addition of N-terminal HIS-tag led to increased formation of trimers. Immunofluorescence staining demonstrated that NcMIF was localized to the apical end of N. caninum tachyzoites. Immunoelectron microscopy further revealed that NcMIF was present in the micronemes, rhoptries, dense granules, and nuclei. NcMIF was abundant in the tachyzoite lysate and present in excretory and secretory antigen (ESAg) preparations. Total and secretory NcMIF was more (P<0.05) abundant in a non-pathologic clone, Ncts-8, than in the wild type isolate (NC1). Furthermore, NcMIF release by the both isolates was increased in the presence of calcium ionophore. This differential production of NcMIF by the pathologic and non-pathologic isolates of N. caninum may suggest a critical role of this molecule in the infectious pathogenesis of this parasite.

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Section: Discussionmentioning

confidence: 92%

Characterization of Neospora caninum macrophage migration inhibitory factor

Qu¹,

Fetterer²,

Jenkins³

et al. 2013

Experimental Parasitology

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“…Among inflammatory mediators, pro-inflammatory cytokine MIF is a particularly interesting candidate. Indeed, MIF has been shown to have an important role in favouring tumorigenesis, and several research groups have shown a correlation between MIF and prognosis in hepatocellular carcinomas, gastric, ovarian, breast, colon, prostate, and non-small cell lung cancers (Meyer-Siegler et al , 1998; Kamimura et al , 2000; Tomiyasu et al , 2002; Legendre et al , 2003; Hira et al , 2005; Lue et al , 2007; Xia et al , 2009). The effect of MIF seems mediated via its binding to CD74 which expression is also linked with several forms of cancer (Datta et al , 2000; Meyer-Siegler et al , 2005, 2006; Binsky et al , 2007; McClelland et al , 2009; Nagata et al , 2009; Verjans et al , 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Apart from its role in inflammation, many factors show that MIF has an important role in promoting tumorigenesis. Migration inhibitory factor is overexpressed in a variety of malignant tumours, such as breast (Lue et al , 2007), colon (Legendre et al , 2003), prostate cancers (Meyer-Siegler et al , 1998), and melanoma (Shimizu et al , 1999), glioblastoma multiform (Bacher et al , 2003) and lung adenocarcinomas (Kamimura et al , 2000; Tomiyasu et al , 2002). It increases tumour growth by favouring tumour cell proliferation and blocking apoptosis; after binding to CD74, it activates the PI3K/Akt pathway.…”

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confidence: 99%

CD74: a new prognostic factor for patients with malignant pleural mesothelioma

et al. 2014

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Background:The pro-inflammatory cytokine migration inhibitory factor (MIF) and its receptor CD74 have been proposed as possible therapeutic targets in several cancers. We studied the expression of MIF and CD74 together with calretinin in specimens of malignant pleural mesothelioma (MPM), correlating their expression levels with clinico-pathologic parameters, in particular overall survival (OS).Methods:Migration inhibitory factor, CD74, and calretinin immunoreactivity were investigated in a tissue microarray of 352 patients diagnosed with MPM. Protein expression intensities were semiquantitatively scored in the tumour cells and in the peritumoral stroma. Markers were matched with OS, age, gender, and histological subtype.Results:Clinical data from 135 patients were available. Tumour cell expressions of MIF and CD74 were observed in 95% and 98% of MPM specimens, respectively, with a homogenous distribution between the different histotypes. CD74 (P<0.001) but not MIF overexpression (P=0.231) emerged as an independent prognostic factor for prolonged OS. High expression of tumour cell calretinin correlated with the epithelioid histotype and was also predictive of longer OS (P<0.001). When compared with previously characterised putative epithelial-to-mesenchymal transition markers, CD74 correlated positively with tumoral PTEN and podoplanin expressions, but was inversely related with periostin expression.Conclusions:High expression of CD74 is an independent prognostic factor for prolonged OS in mesothelioma patients.

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“…In this regard, recent studies indicate that MIF protein levels are elevated in cancer patients [37], [38] and that MIF expression directly correlates with stage, metastatic spread, disease-free survival and tumor-associated neovascularization in e.g. lung, prostate, breast and gastric cancer, as well as glioma patients [37], [39], [40], [41], [42], [43]. Thus, loss of MIF in meningiomas with isolated monosomy 22/del(22q) may also play an important role in determining the more indolent behavior and the good prognosis of this subgroup of meningioma patients.…”

Section: Discussionmentioning

confidence: 99%

Association between Inflammatory Infiltrates and Isolated Monosomy 22/del(22q) in Meningiomas

et al. 2013

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Meningiomas contain highly variable levels of infiltrating tissue macrophages (TiMa) and other immune cells. In this study we investigated the potential association between the number and immunophenotype of inflammatory and other immune cells infiltrating the tumor as evaluated by multiparameter flow cytometry, and the clinico-biological, cytogenetic and gene expression profile (GEP) of 75 meningioma patients. Overall, our results showed a close association between the amount and cellular composition of the inflammatory and other immune cell infiltrates and the cytogenetic profile of the tumors. Notably, tumors with isolated monosomy 22/del(22q) showed greater numbers of TiMa, NK cells and (recently)-activated CD69+ lymphocytes versus meningiomas with diploid and complex karyotypes. In addition, in the former cytogenetic subgroup of meningiomas, tumor-infiltrating TiMa also showed a more activated and functionally mature phenotype, as reflected by a greater fraction of CD69+, CD63+, CD16+ and CD33+ cells. GEP at the mRNA level showed a unique GEP among meningiomas with an isolated monosomy 22/del(22q) versus all other cases, which consisted of increased expression of genes involved in inflammatory/immune response, associated with an M1 TiMa phenotype. Altogether, these results suggest that loss of expression of specific genes coded in chromosome 22 (e.g. MIF) is closely associated with an increased homing and potentially also anti-tumoral effect of TiMa, which could contribute to explain the better outcome of this specific good-prognosis cytogenetic subgroup of meningiomas.

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Intracellular distribution of macrophage migration inhibitory factor predicts the prognosis of patients with adenocarcinoma of the lung

Cited by 136 publications

References 30 publications

Characterization of Neospora caninum macrophage migration inhibitory factor

Characterization of Neospora caninum macrophage migration inhibitory factor

CD74: a new prognostic factor for patients with malignant pleural mesothelioma

Association between Inflammatory Infiltrates and Isolated Monosomy 22/del(22q) in Meningiomas

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