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>3.3.co;2-e

Cited by 45 publications

(61 citation statements)

References 23 publications

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“…Overexpression of MIF has been identified in prostatic lymph node metastases (Meyer-Siegler and Hudson, 1996), human melanomas (Shimizu et al, 1999), breast carcinomas (Bini et al, 1997), adenocarcinomas of the lung (Kamimura et al, 2000), bladder cancer (Meyer-Siegler et al, 2004) and hepatocellular carcinomas (Akbar et al, 2001;Ren et al, 2003a). It has been shown that high levels of MIF significantly correlate with an unfavorable outcome in esophageal squamous cell carcinoma (Ren et al, 2005) and hepatocellular carcinoma (Ren et al, 2003a) and other tumors (del Vecchio et al, 2000;Meyer-Siegler, 2000;Tomiyasu et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of tumor growth and metastasis in vitro and in vivo by targeting macrophage migration inhibitory factor in human neuroblastoma

et al. 2006

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Macrophage migration inhibitory factor (MIF) has been defined as a novel oncogene. Our previous results have shown that MIF may contribute to the progression of neuroblastoma by (a) inducing N-Myc expression and (b) upregulating the expression of angiogenic factors. The aim of this study was to test whether tumor growth could be inhibited by reduction of endogenous MIF expression in neuroblastoma and clarify the molecular mechanisms underlying MIF reduction on the control of neuroblastoma growth. We established human neuroblastoma cell lines stably expressing antisense MIF (AS-MIF) cDNA. These stable transfectants were characterized by cell proliferation, gene expression profile, tumorigenicity and metastasis in vitro and in vivo. Decreased MIF expression was observed after transfection with AS-MIF in neuroblastoma cells and downregulation of MIF expression significantly correlated with decreased expression of NMyc, Ras, c-Met and TrkB at protein level. Affymetrix microarray analysis revealed that expression of IL-8 and c-met was inhibited and neuroblastoma-favorable genes such as EPHB6 and BLU were upregulated in MIF reduced cells. Neuroblastoma cell growth exhibited a nearly 80% reduction in AS-MIF transfectants in vitro. Furthermore, mice in which tumors formed after subcutaneous injection of AS-MIF transfectants showed a 90% reduction in tumor growth compared to control. Metastasis in mice was also suppressed dramatically. Our data demonstrate that targeting MIF expression is a promising therapeutic strategy in human neuroblastoma therapy, and also identifies the MIF target genes for further study.

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Section: Introductionmentioning

confidence: 99%

Inhibition of tumor growth and metastasis in vitro and in vivo by targeting macrophage migration inhibitory factor in human neuroblastoma

et al. 2006

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“…MCM2 has been considered a promising lung tumour marker and perhaps even a marker for premalignant lesions (Tan et al, 2001), whereas tenascin has been proposed as a stromal marker for lung cancer (Kusagawa et al, 1998). Also MIF mRNA and protein levels have been found to be elevated in lung adenocarcinoma specimens (Kamimura et al, 2000) and TOP2A inhibitors are widely used as chemotherapeutic agents in lung cancer treatment (Kellner et al, 2000).…”

Section: Up-regulated Genesmentioning

confidence: 99%

Identification of differentially expressed genes in pulmonary adenocarcinoma by using cDNA array

et al. 2002

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No clear patterns in molecular changes underlying the malignant processes in lung cancer of different histological types have been found so far. To identify critical genes in lung cancer progression we compared the expression profile of cancer related genes in 14 pulmonary adenocarcinoma patients with normal lung tissue by using the cDNA array technique. Principal component analyses (PCA) and permutation test were used to detect the differentially expressed genes. The expression profiles of 10 genes were confirmed by semiquantitative real-time RT -PCR. In tumour samples, as compared to normal lung tissue, the up-regulated genes included such known tumour markers as CCNB1, PLK, tenascin, KRT8, KRT19 and TOP2A. The downregulated genes included caveolin 1 and 2, and TIMP3. We also describe, for the first time, down-regulation of the interesting SOCS2 and 3, DOC2 and gravin. We show that silencing of SOCS2 is not caused by methylation of exon 1 of the gene. In conclusion, by using the cDNA array technique we were able to reveal marked differences in the gene expression level between normal lung and tumour tissue and find possible new tumour markers for pulmonary adenocarcinoma.

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“…Recently, increasing evidence has shown that MIF has a key role not only in the immune response but also in tumor growth and progression. MIF overexpression has been identified in prostatic lymph node metastases, breast carcinoma, adenocarcinomas of the lung, bladder cancer and hepatocellular carcinomas (Meyer-Siegler et al, 1996;Bini et al, 1997;Shimizu et al, 1999;Kamimura et al, 2000;Ren et al, 2003;Meyer-Siegler et al, 2004). A reduction in tumor-associated MIF expression resulted in decreased cell proliferation (Hudson et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Macrophage migration inhibitory factor is a direct target of HBP1-mediated transcriptional repression that is overexpressed in prostate cancer

et al. 2010

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Macrophage migration inhibitory factor (MIF) is a welldescribed proinflammatory mediator. MIF overexpression has been observed in many tumors and is implicated in oncogenic transformation and tumor progression. However, the molecular mechanisms responsible for regulating MIF expression remain poorly understood. In this study, we showed that the transcriptional repressor HBP1 (HMG box-containing protein 1) negatively regulates MIF expression. We first identified a large high-affinity HBP1 DNA-binding element at positions À811 to À792 from the transcriptional start site within the MIF promoter by computer analysis. Reporter analyses showed that this element was required for HBP1-mediated transcriptional repression. Furthermore, HBP1 associated with the MIF promoter in vivo and repressed endogenous MIF gene expression. Consistent with HBP1-mediated repression of MIF, low levels of HBP1 expression were associated with high levels of MIF expression in prostate cancer samples. Importantly, HBP1-mediated repression of MIF inhibited tumorigenic growth and invasion, and the repressive effect of HBP1 on tumorigenic growth and invasion could be partially rescued by the addition of recombinant MIF to the culture medium. Finally, prostate tumor samples with low HBP1 and high MIF expression were associated with a significant decrease in relapse-free survival. Taken together, these results indicated that HBP1 directly inhibited MIF gene transcription, and suggested that the loss of HBP1 expression or activity may contribute to the upregulation of MIF expression in prostate tumor tissue.

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

Abstract: The results of the current study suggest that intracellular MIF distribution predicts patient prognosis in individuals with adenocarcinoma of the lung.

Cited by 45 publications

References 23 publications

Inhibition of tumor growth and metastasis in vitro and in vivo by targeting macrophage migration inhibitory factor in human neuroblastoma

Inhibition of tumor growth and metastasis in vitro and in vivo by targeting macrophage migration inhibitory factor in human neuroblastoma

Identification of differentially expressed genes in pulmonary adenocarcinoma by using cDNA array

Macrophage migration inhibitory factor is a direct target of HBP1-mediated transcriptional repression that is overexpressed in prostate cancer

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