Macrophage migration inhibitory factor in head and neck squamous cell carcinoma: clinical and experimental studies.
OBJECTIVE
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.
Laboratory of Anatomy and Cellular Biology, Faculty of Medicine and Pharmacy, University of Mons, Pentagone 2A, 6 Ave du Champ de Mars, 7000 Mons, Belgium.
Nadège
N
Kindt
Julie
J
Preillon
Herbert
H
Kaltner
Hans-Joachim
HJ
Gabius
Dominique
D
Chevalier
Alexandra
A
Rodriguez
Bryon D
BD
Johnson
Véronique
V
Megalizzi
Christine
C
Decaestecker
Guy
G
Laurent
Sven
S
Saussez
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D009367:Neoplasm Staging; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck; D013601:T-Lymphocytes / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D008263:Macrophage Migration-Inhibitory Factors