title: Deletion of macrophage migration inhibitory factor inhibits murine oral carcinogenesis: Potential role for chronic pro-inflammatory immune mediators.
abstract: Oral cancer kills about 1 person every hour each day in the United States and is the sixth most prevalent cancer worldwide. The pro-inflammatory cytokine 'macrophage migration inhibitory factor' (MIF) has been shown to be expressed in oral cancer patients, yet its precise role in oral carcinogenesis is not clear. In this study, we examined the impact of global Mif deletion on the cellular and molecular process occurring during oral carcinogenesis using a well-established mouse model of oral cancer with the carcinogen 4-nitroquinoline-1-oxide (4NQO). C57BL/6 Wild-type (WT) and Mif knock-out mice were administered with 4NQO in drinking water for 16 weeks, then regular drinking water for 8 weeks. Mif knock-out mice displayed fewer oral tumor incidence and multiplicity, accompanied by a significant reduction in the expression of pro-inflammatory cytokines Il-1β, Tnf-α, chemokines Cxcl1, Cxcl6 and Ccl3 and other molecular biomarkers of oral carcinogenesis Mmp1 and Ptgs2. Further, systemic accumulation of myeloid-derived tumor promoting immune cells was inhibited in Mif knock-out mice. Our results demonstrate that genetic Mif deletion reduces the incidence and severity of oral carcinogenesis, by inhibiting the expression of chronic pro-inflammatory immune mediators. Thus, targeting MIF is a promising strategy for the prevention or therapy of oral cancer.
authors.affiliation: Division of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, OH.|Comprehensive Cancer Center, The Ohio State University, Columbus, OH.
authors.forename: Steve
authors.initials: S
authors.lastname: Oghumu
authors.affiliation: Division of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, OH.|Comprehensive Cancer Center, The Ohio State University, Columbus, OH.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Knobloch
authors.affiliation: Department of Pathology, Ohio State University Medical Center, Columbus, OH.
authors.forename: Cesar
authors.initials: C
authors.lastname: Terrazas
authors.affiliation: Department of Pathology, Ohio State University Medical Center, Columbus, OH.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Varikuti
authors.affiliation: Division of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, OH.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ahn-Jarvis
authors.affiliation: Division of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, OH.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Bollinger
authors.affiliation: Department of Pathology, Ohio State University Medical Center, Columbus, OH.
authors.forename: Hans
authors.initials: H
authors.lastname: Iwenofu
authors.affiliation: Division of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, OH.|Comprehensive Cancer Center, The Ohio State University, Columbus, OH.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Weghorst
authors.affiliation: Department of Pathology, Ohio State University Medical Center, Columbus, OH.
authors.forename: Abhay R
authors.initials: AR
authors.lastname: Satoskar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004195:Disease Models, Animal; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D018655:Lymphocyte Count; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009062:Mouth Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D007155:Immunologic Factors; D018836:Inflammation Mediators; D008263:Macrophage Migration-Inhibitory Factors; D016159:Tumor Suppressor Protein p53
keywords: cancer; cytokine; inflammation; myeloid; oral