Genetic Deletion Of Macrophage Migration Inhibitory Factor Reduces Oral Carcinogenesis

Oral cancer kills about 1 person every hour, each day in the United States and is the 6th 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, Cxcl8 and Ccl3 and other molecular biomarkers of oral carcinogenesis Mmp1 and Ptgs2. Further, recruitment 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 inflammatory cytokines and infiltration of tumor promoting immune cells. Thus, targeting MIF is a promising strategy for the prevention or therapy of oral cancer. Citation Format: Steve Oghumu, Thomas Knobloch, Cesar Terrazas, Sanjay Varikuti, Claire Bollinger, Hans Iwenofu, Christopher Weghorst, Abhay Satoskar. Genetic deletion of macrophage migration inhibitory factor reduces oral carcinogenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3234.