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Erschienen in: Journal of Cancer Research and Clinical Oncology 2/2013

01.02.2013 | Original Paper

Overexpression of macrophage migration inhibitory factor in adenoid cystic carcinoma: correlation with enhanced metastatic potential

verfasst von: Hui Liu, Gang Chen, Wei Zhang, Jun-Yi Zhu, Zhao-Quan Lin, Zhong-Cheng Gong, Feng-Qin Wang, Jun Jia, Zhi-Jun Sun, Yi-Fang Zhao

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 2/2013

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Abstract

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-1α, 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.
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Literatur
Zurück zum Zitat Al-Abed Y, VanPatten S (2011) MIF as a disease target: ISO-I as a proof-of-concept therapeutic. Futur Med Chem 3(1):45–63CrossRef Al-Abed Y, VanPatten S (2011) MIF as a disease target: ISO-I as a proof-of-concept therapeutic. Futur Med Chem 3(1):45–63CrossRef
Zurück zum Zitat Bach JP, Deuster O et al (2009) The role of macrophage inhibitory factor in tumorigenesis and central nervous system tumors. Cancer 115(10):2031–2040PubMedCrossRef Bach JP, Deuster O et al (2009) The role of macrophage inhibitory factor in tumorigenesis and central nervous system tumors. Cancer 115(10):2031–2040PubMedCrossRef
Zurück zum Zitat Balachandran S, Rodge A et al (2009) Novel derivatives of ISO-1 as potent inhibitors of MIF biological function. Bioorg Med Chem Lett 19(16):4773–4776PubMedCrossRef Balachandran S, Rodge A et al (2009) Novel derivatives of ISO-1 as potent inhibitors of MIF biological function. Bioorg Med Chem Lett 19(16):4773–4776PubMedCrossRef
Zurück zum Zitat Bifulco C, McDaniel K et al (2008) Tumor growth-promoting properties of macrophage migration inhibitory factor. Curr Pharm Des 14(36):3790–3801PubMedCrossRef Bifulco C, McDaniel K et al (2008) Tumor growth-promoting properties of macrophage migration inhibitory factor. Curr Pharm Des 14(36):3790–3801PubMedCrossRef
Zurück zum Zitat Bucala R, Donnelly SC (2007) Macrophage migration inhibitory factor: a probable link between inflammation and cancer. Immunity 26(3):281–285PubMedCrossRef Bucala R, Donnelly SC (2007) Macrophage migration inhibitory factor: a probable link between inflammation and cancer. Immunity 26(3):281–285PubMedCrossRef
Zurück zum Zitat Chen G, Hu X et al (2012) Mammalian target of rapamycin regulates isoliquiritigenin-induced autophagic and apoptotic cell death in adenoid cystic carcinoma cells. Apoptosis 17(1):90–101PubMedCrossRef Chen G, Hu X et al (2012) Mammalian target of rapamycin regulates isoliquiritigenin-induced autophagic and apoptotic cell death in adenoid cystic carcinoma cells. Apoptosis 17(1):90–101PubMedCrossRef
Zurück zum Zitat Dodd RL, Slevin NJ (2006) Salivary gland adenoid cystic carcinoma: a review of chemotherapy and molecular therapies. Oral Oncol 42(8):759–769PubMedCrossRef Dodd RL, Slevin NJ (2006) Salivary gland adenoid cystic carcinoma: a review of chemotherapy and molecular therapies. Oral Oncol 42(8):759–769PubMedCrossRef
Zurück zum Zitat Dumitru CA, Gholaman H et al (2011) Tumor-derived macrophage migration inhibitory factor modulates the biology of head and neck cancer cells via neutrophil activation. Int J Cancer 129(4):859–869PubMedCrossRef Dumitru CA, Gholaman H et al (2011) Tumor-derived macrophage migration inhibitory factor modulates the biology of head and neck cancer cells via neutrophil activation. Int J Cancer 129(4):859–869PubMedCrossRef
Zurück zum Zitat Fridman R, Toth M et al (2003) Cell surface association of matrix metalloproteinase-9 (gelatinase B). Cancer Metastasis Rev 22(2–3):153–166PubMedCrossRef Fridman R, Toth M et al (2003) Cell surface association of matrix metalloproteinase-9 (gelatinase B). Cancer Metastasis Rev 22(2–3):153–166PubMedCrossRef
Zurück zum Zitat Heeren PA, Kloppenberg FW et al (2004) Predictive effect of p53 and p21 alteration on chemotherapy response and survival in locally advanced adenocarcinoma of the esophagus. Anticancer Res 24(4):2579–2583PubMed Heeren PA, Kloppenberg FW et al (2004) Predictive effect of p53 and p21 alteration on chemotherapy response and survival in locally advanced adenocarcinoma of the esophagus. Anticancer Res 24(4):2579–2583PubMed
Zurück zum Zitat Huang C, Sun Z et al (2012) Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinoma. Histopathology 60(5):793–803PubMedCrossRef Huang C, Sun Z et al (2012) Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinoma. Histopathology 60(5):793–803PubMedCrossRef
Zurück zum Zitat Jung H, Seong HA et al (2008) Critical role of cysteine residue 81 of macrophage migration inhibitory factor (MIF) in MIF-induced inhibition of p53 activity. J Biol Chem 283(29):20383–20396PubMedCrossRef Jung H, Seong HA et al (2008) Critical role of cysteine residue 81 of macrophage migration inhibitory factor (MIF) in MIF-induced inhibition of p53 activity. J Biol Chem 283(29):20383–20396PubMedCrossRef
Zurück zum Zitat Kleemann R, Hausser A et al (2000) Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1. Nature 408(6809):211–216PubMedCrossRef Kleemann R, Hausser A et al (2000) Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1. Nature 408(6809):211–216PubMedCrossRef
Zurück zum Zitat Krockenberger M, Engel JB et al (2010) Macrophage migration inhibitory factor expression in cervical cancer. J Cancer Res Clin Oncol 136(5):651–657PubMedCrossRef Krockenberger M, Engel JB et al (2010) Macrophage migration inhibitory factor expression in cervical cancer. J Cancer Res Clin Oncol 136(5):651–657PubMedCrossRef
Zurück zum Zitat Lue H, Dewor M et al (2011) Activation of the JNK signalling pathway by macrophage migration inhibitory factor (MIF) and dependence on CXCR4 and CD74. Cell Signal 23(1):135–144PubMedCrossRef Lue H, Dewor M et al (2011) Activation of the JNK signalling pathway by macrophage migration inhibitory factor (MIF) and dependence on CXCR4 and CD74. Cell Signal 23(1):135–144PubMedCrossRef
Zurück zum Zitat Meyer-Siegler KL, Iczkowski KA et al (2006) Inhibition of macrophage migration inhibitory factor or its receptor (CD74) attenuates growth and invasion of DU-145 prostate cancer cells. J Immunol 177(12):8730–8739PubMed Meyer-Siegler KL, Iczkowski KA et al (2006) Inhibition of macrophage migration inhibitory factor or its receptor (CD74) attenuates growth and invasion of DU-145 prostate cancer cells. J Immunol 177(12):8730–8739PubMed
Zurück zum Zitat Nabizadeh Marvast M, Sima HR et al (2011) Clinicopathological significance of macrophage migration inhibitory factor and its relation with p53 in gastric cancer. J Gastrointest Cancer 42(1):5–10PubMedCrossRef Nabizadeh Marvast M, Sima HR et al (2011) Clinicopathological significance of macrophage migration inhibitory factor and its relation with p53 in gastric cancer. J Gastrointest Cancer 42(1):5–10PubMedCrossRef
Zurück zum Zitat Oda S, Oda T et al (2008) Macrophage migration inhibitory factor activates hypoxia-inducible factor in a p53-dependent manner. PLoS ONE 3(5):e2215PubMedCrossRef Oda S, Oda T et al (2008) Macrophage migration inhibitory factor activates hypoxia-inducible factor in a p53-dependent manner. PLoS ONE 3(5):e2215PubMedCrossRef
Zurück zum Zitat Piao S, Zhao S et al (2012) Increased expression of CD147 and MMP-9 is correlated with poor prognosis of salivary duct carcinoma. J Cancer Res Clin Oncol 138(4):627–635PubMedCrossRef Piao S, Zhao S et al (2012) Increased expression of CD147 and MMP-9 is correlated with poor prognosis of salivary duct carcinoma. J Cancer Res Clin Oncol 138(4):627–635PubMedCrossRef
Zurück zum Zitat Qi D, Hu X et al (2009) Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion. J Clin Invest 119(12):3807–3816PubMedCrossRef Qi D, Hu X et al (2009) Cardiac macrophage migration inhibitory factor inhibits JNK pathway activation and injury during ischemia/reperfusion. J Clin Invest 119(12):3807–3816PubMedCrossRef
Zurück zum Zitat Rendon BE, Roger T et al (2007) Regulation of human lung adenocarcinoma cell migration and invasion by macrophage migration inhibitory factor. J Biol Chem 282(41):29910–29918PubMedCrossRef Rendon BE, Roger T et al (2007) Regulation of human lung adenocarcinoma cell migration and invasion by macrophage migration inhibitory factor. J Biol Chem 282(41):29910–29918PubMedCrossRef
Zurück zum Zitat Rendon BE, Willer SS et al (2009) Mechanisms of macrophage migration inhibitory factor (MIF)-dependent tumor microenvironmental adaptation. Exp Mol Pathol 86(3):180–185PubMedCrossRef Rendon BE, Willer SS et al (2009) Mechanisms of macrophage migration inhibitory factor (MIF)-dependent tumor microenvironmental adaptation. Exp Mol Pathol 86(3):180–185PubMedCrossRef
Zurück zum Zitat Salminen A, Kaarniranta K (2011) Control of p53 and NF-kappaB signaling by WIP1 and MIF: role in cellular senescence and organismal aging. Cell Signal 23(5):747–752PubMedCrossRef Salminen A, Kaarniranta K (2011) Control of p53 and NF-kappaB signaling by WIP1 and MIF: role in cellular senescence and organismal aging. Cell Signal 23(5):747–752PubMedCrossRef
Zurück zum Zitat Spiro RH (1997) Distant metastasis in adenoid cystic carcinoma of salivary origin. Am J Surg 174(5):495–498PubMedCrossRef Spiro RH (1997) Distant metastasis in adenoid cystic carcinoma of salivary origin. Am J Surg 174(5):495–498PubMedCrossRef
Zurück zum Zitat Sun ZJ, Chen G et al (2010a) Activation of PI3 K/Akt/IKK-alpha/NF-kappaB signaling pathway is required for the apoptosis-evasion in human salivary adenoid cystic carcinoma: its inhibition by quercetin. Apoptosis 15(7):850–863PubMedCrossRef Sun ZJ, Chen G et al (2010a) Activation of PI3 K/Akt/IKK-alpha/NF-kappaB signaling pathway is required for the apoptosis-evasion in human salivary adenoid cystic carcinoma: its inhibition by quercetin. Apoptosis 15(7):850–863PubMedCrossRef
Zurück zum Zitat Sun ZJ, Chen G et al (2010b) Mammalian target of rapamycin pathway promotes tumor-induced angiogenesis in adenoid cystic carcinoma: its suppression by isoliquiritigenin through dual activation of c-Jun NH2-terminal kinase and inhibition of extracellular signal-regulated kinase. J Pharmacol Exp Ther 334(2):500–512PubMedCrossRef Sun ZJ, Chen G et al (2010b) Mammalian target of rapamycin pathway promotes tumor-induced angiogenesis in adenoid cystic carcinoma: its suppression by isoliquiritigenin through dual activation of c-Jun NH2-terminal kinase and inhibition of extracellular signal-regulated kinase. J Pharmacol Exp Ther 334(2):500–512PubMedCrossRef
Zurück zum Zitat Sun ZJ, Chen G et al (2011) Curcumin dually inhibits both mammalian target of rapamycin and nuclear factor-kappaB pathways through a crossed phosphatidylinositol 3-kinase/Akt/IkappaB kinase complex signaling axis in adenoid cystic carcinoma. Mol Pharmacol 79(1):106–118PubMedCrossRef Sun ZJ, Chen G et al (2011) Curcumin dually inhibits both mammalian target of rapamycin and nuclear factor-kappaB pathways through a crossed phosphatidylinositol 3-kinase/Akt/IkappaB kinase complex signaling axis in adenoid cystic carcinoma. Mol Pharmacol 79(1):106–118PubMedCrossRef
Zurück zum Zitat Suzuki F, Nakamaru Y et al (2005) Prognostic significance of cytoplasmic macrophage migration inhibitory factor expression in patients with squamous cell carcinoma of the head and neck treated with concurrent chemoradiotherapy. Oncol Rep 13(1):59–64PubMed Suzuki F, Nakamaru Y et al (2005) Prognostic significance of cytoplasmic macrophage migration inhibitory factor expression in patients with squamous cell carcinoma of the head and neck treated with concurrent chemoradiotherapy. Oncol Rep 13(1):59–64PubMed
Zurück zum Zitat Tang Y, Liang X et al (2010) Expression of c-kit and Slug correlates with invasion and metastasis of salivary adenoid cystic carcinoma. Oral Oncol 46(4):311–316PubMedCrossRef Tang Y, Liang X et al (2010) Expression of c-kit and Slug correlates with invasion and metastasis of salivary adenoid cystic carcinoma. Oral Oncol 46(4):311–316PubMedCrossRef
Zurück zum Zitat Wagner EF, Nebreda AR (2009) Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer 9(8):537–549PubMedCrossRef Wagner EF, Nebreda AR (2009) Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer 9(8):537–549PubMedCrossRef
Zurück zum Zitat Winner M, Koong AC et al (2007) Amplification of tumor hypoxic responses by macrophage migration inhibitory factor-dependent hypoxia-inducible factor stabilization. Cancer Res 67(1):186–193PubMedCrossRef Winner M, Koong AC et al (2007) Amplification of tumor hypoxic responses by macrophage migration inhibitory factor-dependent hypoxia-inducible factor stabilization. Cancer Res 67(1):186–193PubMedCrossRef
Metadaten
Titel
Overexpression of macrophage migration inhibitory factor in adenoid cystic carcinoma: correlation with enhanced metastatic potential
verfasst von
Hui Liu
Gang Chen
Wei Zhang
Jun-Yi Zhu
Zhao-Quan Lin
Zhong-Cheng Gong
Feng-Qin Wang
Jun Jia
Zhi-Jun Sun
Yi-Fang Zhao
Publikationsdatum
01.02.2013
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 2/2013
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-012-1330-z

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