title: Pharmacological inhibition of macrophage migration inhibitory factor interferes with the proliferation and invasiveness of squamous carcinoma cells.
abstract: Recent clinical observations and experimental studies of our group indicate that macrophage migration inhibitory factor (MIF) may contribute to tumor progression in head and neck squamous cell carcinomas (HNSCC). The present study was undertaken to examine the effects of the irreversible MIF inhibitor 4-iodo-6-phenylpyrimidine (4-IPP) on proliferation and invasiveness of the squamous carcinoma cell line SCCVII. Cell counting, crystal violet assay and flow cytometry were used to analyze the effects of 4-IPP on SCCVII cell growth. The impact of 4-IPP on cell invasiveness was assessed by Boyden chamber assay. Knockdown of the MIF receptor CD74 was achieved by transduction with lentiviral vectors encoding anti-CD74 shRNAs. As shown by immunofluorescence staining, SCCVII cells express both MIF and CD74. Decreased MIF immunoreactivity as a result of exposure to 4-IPP suggested a covalent modification of the cytokine. 4-IPP inhibited SCCVII cell proliferation and invasiveness. Moreover, the cytostatic effect of 4-IPP was enhanced by CD74 knockdown. The inhibitory effects of 4-IPP on cell proliferation and invasiveness strongly suggest that MIF is involved in proliferative activity and invasive properties of squamous carcinoma cells. In conclusion, MIF inhibition may open possibilities for target-directed treatment of head and neck squamous cell carcinoma.
authors.affiliation: Laboratory of Anatomy and Cellular Biology, Faculty of Medicine and Pharmacy, University of Mons, 7000 Mons, Belgium.
authors.forename: Nadège
authors.initials: N
authors.lastname: Kindt
authors.forename: Guy
authors.initials: G
authors.lastname: Laurent
authors.forename: Denis
authors.initials: D
authors.lastname: Nonclercq
authors.forename: Fabrice
authors.initials: F
authors.lastname: Journé
authors.forename: Ghanem
authors.initials: G
authors.lastname: Ghanem
authors.forename: Hugues
authors.initials: H
authors.lastname: Duvillier
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lechien
authors.forename: Sven
authors.initials: S
authors.lastname: Saussez
mesh_terms: D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology
chemical_list: C532251:4-iodo-6-phenylpyrimidine; D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; D011743:Pyrimidines; C045084:invariant chain