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Macrophage migration inhibitory factor in head and neck squamous cell carcinoma: clinical and experimental studies

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Abstract

Purpose

The present in vivo/in vitro study was undertaken in order to evaluate the importance of macrophage migration inhibitory factor (MIF) in the progression of head and neck squamous cell carcinoma (HNSCC).

Methods

Tumor tissue expression (MIF immunostaining) and plasma levels (ELISA) of MIF were determined in HNSCC patients and correlated with tumor recurrence and metastasis, and overall survival. Furthermore, the impact of MIF expression on cell proliferation and anticancer drug sensitivity was examined in murine squamous carcinoma cell line SCCVII after MIF knockdown (MIF-KD).

Results

As revealed by quantitative analysis of MIF immunostaining, tumor progression was accompanied by an increase in mean optical density (MOD) and labeling index (LI). Likewise, an elevation of MIF serum levels was noted in HNSCC patients (n = 66) versus healthy individuals (n = 16). Interestingly, comparison of laryngeal carcinoma patients on the basis of MIF tissue expression (high expression, LI ≥ 47, versus low expression, LI < 47) disclosed a significant difference between disease-free survival curves for local and nodal recurrence, and overall survival curve. In vitro, MIF knockdown in murine SCCVII cells resulted in reduced cell proliferation and a decrease in cell motility. In mice inoculated with SCCVII cells, MIF-KD tumors grew more slowly and also appeared more sensitive to chemotherapy.

Conclusions

Both clinical observations and experimental data suggest that MIF plays a pivotal role in the progression of HNSCC.

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References

  • Bruchfeld A, Carrero JJ, Qureshi AR, Lindholm B, Barany P, Heimburger O et al (2009) Elevated serum macrophage migration inhibitory factor (MIF) concentrations in chronic kidney disease (CKD) are associated with markers of oxidative stress and endothelial activation. Mol Med 15:70–75

    Article  PubMed  CAS  Google Scholar 

  • Camlica H, Duranyildiz D, Oguz H, Oral EN, Yasasever V (2008) The diagnostic value of macrophage migration inhibitory factor (MIF) in gastric cancer. Pathol Oncol Res 14:79–83

    Article  PubMed  CAS  Google Scholar 

  • Chen RJ, Deng WG, Niu CB, Li YY, Fu Y (2011) Expression of macrophage migration inhibitory factor and CD74 in cervical squamous cell carcinoma. Int J Gynecol Cancer 21:1004–1012

    Article  CAS  Google Scholar 

  • Cludts S, Decaestecker C, Johnson B, Lechien J, Leroy X, Kindt N, Kaltner H, André S, Gabius HJ, Saussez S (2010) Increased expression of macrophage migration inhibitory factor during progression to hypopharyngeal squamous cell carcinoma. Anticancer Res 30:3313–3319

    PubMed  Google Scholar 

  • Conroy H, Mawhinney L, Donnelly SC (2010) Inflammation and cancer: macrophage migration inhibitory factor (MIF)–the potential missing link. QJM 103:831–836

    Article  PubMed  CAS  Google Scholar 

  • Debeir O, Van Ham P, Kiss R, Decaestecker C (2005) Tracking of migrating cells under phase-contrast video microscopy with combined mean-shift processes. IEEE Trans Med Imaging 24:697–711

    Article  PubMed  CAS  Google Scholar 

  • Debeir O, Megalizzi V, Warzée N, Kiss R, Decaestecker C (2008) Videomicroscopic extraction of specific information on cell proliferation and migration in vitro. Exp Cell Res 314:2985–2998

    Article  PubMed  CAS  Google Scholar 

  • Dumitru CA, Gholaman H, Trellakis S, Bruderek K, Dominas N, Gu X, Bankfalvi A, Whiteside TL, Lang S, Brandau S (2011) Tumor-derived macrophage migration inhibitory factor modulates the biology of head and neck cancer cells via neutrophil activation. Int J Cancer 129:859–869

    Article  PubMed  CAS  Google Scholar 

  • Filleul O, Preillon J, Crompot E, Lechien J, Saussez S (2011) Incidence of head and neck cancers in Belgium: comparison with worldwide and French data. Bull Cancer 10:1173–1183

    Google Scholar 

  • Hagemann T, Robinson SC, Thompson RG, Charles K, Kulbe H, Balkwill FR (2007) Ovarian cancer cell-derived migration inhibitory factor enhances tumor growth, progression, and angiogenesis. Mol Cell Ther 6:1993–2002

    CAS  Google Scholar 

  • He XX, Chen K, Yang J, Li XY, Gan HY, Liu CY, Coleman TR, Al-Abed Y (2009) Macrophage migration inhibitory factor promotes colorectal cancer. Mol Med 15:1–10

    Article  PubMed  CAS  Google Scholar 

  • Hira E, Ono T, Dhar DK, El-Assal ON, Hishikawa Y, Yamanoi A, Nagasue N (2005) Overexpression of macrophage migration inhibitory factor induces angiogenesis and deteriorates prognosis after radical resection for hepatocellular carcinoma. Cancer 103:588–598

    Article  PubMed  CAS  Google Scholar 

  • Hyams VJ, Batsakis JG, Michaels L (1988) Tumors of the Upper Respiratory Tract and Ear. In Atlas of Tumor Pathology, Washington DC, Armed Forces Institute of Pathology, pp 123–126

    Google Scholar 

  • Kamimura A, Kamachi M, Nishihira J, Ogura S, Isobe H, Dosaka-Akita H, Ogata A, Shindoh M, Ohbuchi T, Kawakami Y (2000) Intracellular distribution of macrophage migration inhibitory factor predicts the prognosis of patients with adenocarcinoma of the lung. Cancer 89:334–341

    Article  PubMed  CAS  Google Scholar 

  • Krockenberger M, Engel JB, Kolb J, Dombrowsky Y, Häusler SF, Kohrenhagen N, Dietl J, Wischhusen J, Honig A (2010) Macrophage migration inhibitory factor expression in cervical cancer. J Cancer Res Clin Oncol 136:651–657

    Article  PubMed  CAS  Google Scholar 

  • Lee H, Rhee H, Kang HJ, Kim HS, Min BS, Kim NK et al (2008) Macrophage migration inhibitory factor may be used as an early diagnostic marker in colorectal carcinomas. Am J Clin Pathol 129:772–779

    Article  PubMed  Google Scholar 

  • Leng L, Bucala R (2006) Insight into the biology of macrophage migration inhibitory factor (MIF) revealed by the cloning of its cell surface receptor. Cell Res 16:162–168

    Article  PubMed  CAS  Google Scholar 

  • Li Z, Ren Y, Wu QC, Lin SX, Liang YJ, Liang HZ (2004) Macrophage migration inhibitory factor enhances neoplastic cell invasion by inducing the expression of matrix metalloproteinase 9 and interleukin-8 in nasopharyngeal carcinoma cell lines. Chin Med J 117:107–114

    PubMed  CAS  Google Scholar 

  • Lue H, Kleemann R, Calandra T, Roger T, Bernhagen J (2002) Macrophage migration inhibitory factor (MIF): mechanisms of action and role in disease. Microbes Infect 4:449–460

    Article  PubMed  CAS  Google Scholar 

  • Mitchell RA (2004) Mechanisms and effectors of MIF-dependent promotion of tumourigenesis. Cell Signal 16:13–19

    Article  PubMed  CAS  Google Scholar 

  • O’Malley BW Jr, Cope KA, Johnson CS, Schwartz MR (1997) A new immunocompetent murine model for oral cancer. Arch Otolaryngol Head Neck Surg 123:20–24

    Article  PubMed  Google Scholar 

  • Ren Y, Law S, Huang X, Lee PY, Bacher M, Srivastava G, Wong J (2005) Macrophage migration inhibitory factor stimulates angiogenic factor expression and correlates with differentiation and lymph node status in patients with esophageal squamous cell carcinoma. Ann Surg 242:55–63

    Article  PubMed  Google Scholar 

  • Rendon BE, Roger T, Teneng I, Zhao M, Al-Abed Y, Calandra T, Mitchell RA (2007) Regulation of human lung adenocarcinoma cell migration and invasion by macrophage migration inhibitory factor. J Biol Chem 282:29910–29918

    Article  PubMed  CAS  Google Scholar 

  • Rendon BE, Willer SS, Zundel W, Mitchell RA (2009) Mechanisms of macrophage migration inhibitory factor (MIF)-dependent tumor microenvironmental adaptation. Exp Mol Pathol 86:180–185

    Article  PubMed  CAS  Google Scholar 

  • Santos LL, Morand EF (2008) Macrophage migration inhibitory factor: a key cytokine in RA, SLE and atherosclerosis. Clin Chim Acta 399:1–7

    Article  PubMed  Google Scholar 

  • Saussez S, Cucu DR, Decaestecker C, Chevalier D, Kaltner H, André S, Wacreniez A, Toubeau G, Camby I, Gabius HJ, Kiss R (2006) Galectin 7 (p53-induced gene 1): a new prognostic predictor of recurrence and survival in stage IV hypopharyngeal cancer. Ann Surg Oncol 13:999–1009

    Article  PubMed  Google Scholar 

  • Shi X, Leng L, Wang T, Wang W, Du X, Li J, McDonald C, Chen Z, Murphy JW, Lolis E, Noble P, Knudson W, Bucala R (2006) CD44 is the signaling component of the macrophage migration inhibitory factor-CD74 receptor complex. Immunity 25:595–606

    Article  PubMed  CAS  Google Scholar 

  • Suzuki F, Nakamaru Y, Oridate N, Homma A, Nagahashi T, Yamaguchi S, Nishihira J, Furuta Y, Fukuda S (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 13:59–64

    PubMed  Google Scholar 

  • Wang X-B, Tian X-Y, Li Y, Li B, Li Z (2012) Elevated expression of macrophage migration inhibitory factor correlates with tumor recurrence and poor prognosis of patients with gliomas. J Neurooncol 106:43–51

    Article  PubMed  Google Scholar 

  • Wittekind C, Greene FL, Hutter RVP (2004) TNM atlas. 5th ed. pp 20–32. UICC Springer: Berlin

  • Xiao DZ, Dai B, Chen J, Luo Q, Liu XY, Lin QX, Li XH, Huang W, Yu XY (2011) Loss of macrophage migration inhibitory factor impairs the growth properties of human HeLa cervical cancer cells. Cell Prolif 44:582–590

    Article  PubMed  CAS  Google Scholar 

  • Yan X, Orentas RJ, Johnson BD (2006) Tumor-derived macrophage migration inhibitory factor (MIF) inhibits T lymphocyte activation. Cytokine 33:188–198

    Article  PubMed  CAS  Google Scholar 

  • Zeng F-Y, Weiser WY, Kratzin H, Stahl B, Karas M, Gabius HJ (1993) The major binding protein of the interferon antagonist sarcolectin in human placenta is a macrophage migration inhibitory factor? Arch Biochem Biophys 303:74–80

    Article  PubMed  CAS  Google Scholar 

  • Zhou Q, Yan X, Gershan J, Orentas RJ, Johnson BD (2008) Expression of macrophage migration inhibitory factor by neuroblastoma leads to the inhibition of antitumor T cell reactivity in vivo. J Immunol 181:1877–1886

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

NK is the recipient of a fellowship from the “Fondation Rose and Jean Hoguet.” CD and GL are Senior Research Associates of the National Fund for Scientific Research (Belgium). GL is the recipient of a grant from the Belgian Fund for Medical Scientific Research. Taxotere was a kind gift from Sanofi-Aventis.

Conflict of interest

The authors declare no conflict of interest.

Author information

Author notes

  1. Julie Preillon

    Present address: Laboratory of Developmental Genetics, Institute of Molecular Biology and Medicine (IBMM), Université Libre de Bruxelles (ULB), 12 Rue des Professeurs Jeener et Brachet, 6041, Gosselies, Belgium

Authors and Affiliations

  1. Laboratory of Anatomy and Cellular Biology, Faculty of Medicine and Pharmacy, University of Mons (UMons), Pentagone 2A, 6 Ave du Champ de Mars, 7000, Mons, Belgium

    Nadège Kindt, Julie Preillon & Sven Saussez

  2. Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig Maximilians University, 80539, Munich, Germany

    Herbert Kaltner & Hans-Joachim Gabius

  3. Department of Oto-Rhino-Laryngology, Faculty of Medicine, Hôpital Claude Huriez and Centre de Biologie-Pathologie-CHRU, 1 Place de Verdun, 59037, Lille, France

    Dominique Chevalier

  4. Department of Oto-Rhino-Laryngology, Faculty of Medicine, Université Libre de Bruxelles (ULB), CHU St-Pierre, rue haute 322, 1000, Brussels, Belgium

    Alexandra Rodriguez & Sven Saussez

  5. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, 53226, USA

    Bryon D. Johnson

  6. Laboratory of Toxicology, Faculty of Pharmacy, Université Libre de Bruxelles (ULB), CP205/01Bouvelard du Triomphe, 1050, Brussels, Belgium

    Véronique Megalizzi

  7. Laboratory of Image Synthesis and Analysis, Ecole Polytechnique de Bruxelles, 50 Ave F.D. Roosevelt, 1050, Brussels, Belgium

    Christine Decaestecker

  8. Laboratory of Histology, Faculty of Medicine and Pharmacy, University of Mons, 6 Ave du Champ de Mars, 7000, Mons, Belgium

    Guy Laurent

Authors
  1. Nadège Kindt
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  2. Julie Preillon
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  3. Herbert Kaltner
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  6. Alexandra Rodriguez
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  7. Bryon D. Johnson
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  8. Véronique Megalizzi
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  11. Sven Saussez
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Corresponding author

Correspondence to Sven Saussez.

Additional information

Nadège Kindt and Julie Preillon contributed equally to this study and should be considered as joint First Authors.

Guy Laurent and Sven Saussez wish it to be known that, in their opinion, the last 2 authors should be regarded as joint Last Authors.

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Kindt, N., Preillon, J., Kaltner, H. et al. Macrophage migration inhibitory factor in head and neck squamous cell carcinoma: clinical and experimental studies. J Cancer Res Clin Oncol 139, 727–737 (2013). https://doi.org/10.1007/s00432-013-1375-7

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  • DOI: https://doi.org/10.1007/s00432-013-1375-7

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