4282

MIF

macrophage migration inhibitory factor (glycosylation-inhibiting factor);MIF;macrophage migration inhibitory factor (glycosylation-inhibiting factor)

L-dopachrome isomerase|L-dopachrome tautomerase|macrophage migration inhibitory factor|phenylpyruvate tautomerase

22q11.23

protein-coding

OBJECTIVES: Adenoid cystic carcinoma (ACC) is a malignant tumor frequently arising in salivary glands with poor long-term prognosis due to high rates of local recurrences and distant metastases. Macrophage migration inhibitory factor (MIF) is a multi-functional cytokine and has recently emerged as a pro-tumorigenic factor in various cancers. This study is designed to investigate the expression status and functional significance of MIF in ACC. METHODS: Immunohistochemical staining was performed to evaluate the expression levels of MIF, HIF-1alpha, MMP-9, p53, and p-JNK in ACC tissues. In vitro, ACC-2 cells were exposed to recombinant human MIF (rMIF) or ISO-1 (an inhibitor of MIF) at different concentrations and times, followed by the detection of cell growth, viability, migration, and invasion, as well as the expression levels of several cellular signals. RESULTS: The immunohistochemical results demonstrated the overexpression of MIF in ACC tissues as well as its association with the distant metastasis. Further analyses showed a significant correlation between the staining of MIF and p-JNK. Moreover, the in vitro studies revealed that the treatment for ACC cells with ISO-1 significantly attenuated cell migratory and invasive capacity, as opposed to the limited promotive effects of rMIF. More importantly, MIF inhibition could cause the activation of JNK, correlating with the immunohistochemical findings on ACC tissues. CONCLUSIONS: The results suggest that MIF is likely to be an important player in the pathogenesis of ACC and may promote cancer metastasis, which possibly involves JNK inactivation. Further investigation of MIF-mediated molecular events may provide novel insights into the treatment for ACC.

metastasis of cancer cells is a major cause of death in cancer patients. The process of cancer metastasis includes the proliferation of primary cancer cells, local invasion, intravasation and cancer cell survival in blood flow, extravasation and attachment to secondary organs and metastatic growth in a new environment. In these mechanisms of cancer metastasis, CXC chemokine receptor 4 (CXCR4) and its ligand play an important role. Stromal cell-derived factor-1alpha (SDF-1alpha, also known as CXCL12) is well known as a ligand of CXCR4, and macrophage migration-inhibitory factor (MIF) has recently become known as a ligand of CXCR4. In many types of cancers including breast, pancreatic and colorectal cancer (CRC), CXCR4/SDF-1alpha has been investigated in metastasis-related cancer behavior, which include cell proliferation, adhesion, migration and invasion. However, CXCR4/MIF has rarely been investigated in the metastatic behavior of colon cancer cells. In this report, the effect of SDF-1alpha or MIF was studied on cell cycle, cell proliferation, adhesion and migration of the CXCR4-expressing colon cancer cell line SW480. SDF-1alpha or MIF caused a decrease in the number of cells in G0/G1 phase and an increase in the numbers of cells in S and G2/M phases. In addition, SDF-1alpha or MIF caused an increase in cell proliferation, cell adhesion to fibronectin and migration. AMD3100, a CXCR4 antagonist, attenuated these effects, which included increased cell proliferation, adhesion and migration due to treatment of CXCR4-expressing colon cancer cells with SDF-1alpha or MIF. In conclusion, SDF-1alpha or MIF affects the metastasis-related behaviors of CXCR4-expressing colon cancer cells.

OBJECTIVE: To explore the possible relationship between the expressions of macrophage migration inhibitor factor (MIF), cyclin D1, cyclin-dependent kinase 4 (CDK4), phosphorylated-retinoblastoma susceptibility gene product Rb protein (phospho-Rb) and the development of hepatocellular carcinoma (HCC). METHODS: 93 HCC tissues and 5 normal liver tissues were used to investigate the expressions of MIF, cyclin D1, CDK4 and phospho-Rb by tissue microarray and immunohistochemistry methods. RESULTS: The expression rates of MIF, cyclin D1, CDK4 and phospho-Rb in the HCC tissues were 71%, 41%, 82% and 14% respectively, and in the normal liver tissues, they were 0%, 0%, 80% and 20% respectively. The expression rates of MIF and cyclin D1 were significantly different between the tumor and the normal liver tissues and the expression rates of CDK4 and phospho-Rb were not significantly different between the tumor and the normal liver tissues. The rate difference (69% versus 48%) of MIF expression between the larger tumors (> 3.5 cm) and the smaller tumors (< 3.5 cm) was of statistical significance (P < 0.01). The expression rate (62%) of cyclin D1 in the tumors with metastasis was significantly higher than the expression rate (35%) in the tumors without metastasis (P < 0.05). MIF expression was positively correlated with cyclin D1 expression in the tumor tissues (P < 0.01). CDK4 and phospho-Rb expressions were not significantly associated with the tumor sizes and metastasis status. CONCLUSION: Our results indicate that MIF and cyclin D1 might be related to the growth and metastasis of HCC.

BACKGROUND AND OBJECTIVES: We aim at the association of macrophage migration inhibitory factor (MIF) with neovascularization and survival of nasopharyngeal carcinoma (NPC), and determine whether MIF is a valuable prognostic predictor for NPC patients. METHODS: One hundred and forty one cases of NPC and 25 normal tissues of nasopharynx were collected. The expression of MIF and interleukin 8 (IL-8) was evaluated in tissues microarray by immunostaining. Intratumoral microvessel density (IMD) in relation to immunostainings and clinicopathological factors were analyzed statistically as well as the follow-up data of patients. RESULTS: High-expression of both MIF (69.5%) and IL-8 (56.0%) were significantly associated with increased microvessels and lymph node metastasis. High-expression of MIF, IL-8 and higher level of IMD were correlated with either patients' overall survival or disease-specific survival in univariate analysis, but only angiogenesis and lymph node status exhibited in relation to survival of patients as independent prognostic factor of NPC by multivariate analysis. In addition, high-expression of MIF and higher level of IMD were closely associated with locoregional failure of NPC patients. CONCLUSIONS: MIF may contribute to lymph node metastasis in NPC by inducing angiogenesis through the way of upregulation of IL-8 expression in an autocrine EBV-independent pathway.

BACKGROUND AND AIM: Both macrophage migration inhibitory factor (MIF) and DJ-1 protein have been shown to relate with cell invasion and metastasis in tumors. However, the role of DJ-1 in invasion and metastasis of nasopharyngeal carcinoma (NPC) and its relation to MIF expression in NPC are not fully understood. The aim of present study is to determine whether or not MIF and DJ-1 are correlated with tumor invasion and influence a worse outcome in NPC, as well as its related mechanism. METHODS: 125 cases of NPC and 45 normal tissues of nasopharynx were collected. The expression of MIF and DJ-1 in tissue microarray was evaluated by immunohistochemical staining. Correlation between immunostainings and clinicopathological parameters, as well as the follow-up data of patients, was analyzed statistically. The association of MIF and DJ-1 with cell invasion and migration in NPC cell line were evaluated by small interfering RNA (siRNA) transfection, invasion assay and Western blotting. RESULTS: MIF and DJ-1 staining was diffused and strong in tumor cells, whereas they were generally weaker and less common in normal lining epithelia of nasopharynx. High MIF expression in tumor cells (71.2%, 89/125 cases) were significantly associated with advanced clinical stage, lymph node metastasis, and worse prognosis of NPC patients. High expression of DJ-1 (75.2%, 94/125 cases) were closely correlated to lymph node metastasis and MIF high-expression. Only MIF high expression (P = 0.010) and lymph node metastasis (P = 0.004) emerged as strong independent prognostic factors for overall survival of NPC patients. In vitro, down-regulated expression of DJ-1 in NPC cell lines by siRNA was observed to reduce cell migration and invasion potential, however, exogenous MIF promoted cells invasion. CONCLUSIONS: The data provided evidence that increased expression of MIF and DJ-1 induced cell invasion and metastasis of NPC, supporting the idea that MIF and DJ-1 may play important roles as regulators in the progression of NPC.

OBJECTIVE: To investigate the expression of macrophage migration inhibitory factor (MIF) and extracellular matrix metalloproteinase inducer (CD147) in non-small cell lung cancer (NSCLC) and its metastatic lymph node with tissue microarray technique, and to reveal clinical significance of these two molecules expression in NSCLC. METHODS: MIF and CD147 proteins were detected in 40 cases of benign pulmonary tissues, 327 cases of primary NSCLC and 112 cases of lymph node metastatic tissues by SP method of immunohistochemical staining. RESULTS: The expression of both MIF and CD147 in benign pulmonary tissues, NSCLC primary foci and metastatic lymph node appeared upward tendency (P < 0.05). Furthermore, expression level of MIF and CD147 proteins in NSCLC were related to the metastasis (P < 0.05) and TNM staging (P < 0.05). The Spearman correlation analysis showed that the expression of MIF and CD147 was positively correlated (r = 0.400, P = 0.000). Kaplan-Meier survival analysis indicated that the survival rate was markedly lower in patients with high expression level of MIF or CD147 than those with low expression level (P < 0.05). Multivariate analysis using Cox regression model identified that pathologic grading, metastasis, TNM staging and CD147 expression were independent prognostic factors of NSCLC patients (P < 0.05). CONCLUSION: MIF and CD147 may play important roles in invasion and metastasis in NSCLC, so might be employed to evaluate the prognosis of NSCLC patients.