Oral squamous carcinoma cells promote macrophage polarization in an MIF-dependent manner

Author(s)

de Souza Rizzo, M. Barbosa ^{[1, 2, 3]} ; Brasilino de Carvalho, M. ^{[1, 2]} ; Kim, E. J. ^[3] ; Rendon, B. E. ^[3] ; Noe, J. T. ^{[3, 4]} ; Wise, A. Darlene ^{[3, 5]} ; Mitchell, R. A. ^{[3, 4, 5, 6]}

Affiliation

^[1] Univ Sao Paulo, Med Sch, Dept Radiol & Oncol, Sao Paulo, SP - Brazil

^[2] Heliopolis Hosp, Lab Mol Biol, Sao Paulo, SP - Brazil

^[3] Univ Louisville, JG Brown Canc Ctr, Louisville, KY 40292 - USA

^[4] Univ Louisville, Dept Biochem & Mol Genet, Louisville, KY 40292 - USA

^[5] Univ Louisville, Dept Microbiol & Immunol, Louisville, KY - USA

^[6] Univ Louisville, Dept Med, Louisville, KY 40292 - USA

• Document type: Journal article
• Source: QJM-AN INTERNATIONAL JOURNAL OF MEDICINE; v. 111, n. 11, p. 769-778, NOV 2018.
• Web of Science Citations: 0

Abstract

Background: Tumor-associated macrophages (TAMs) are important determinants of intratumoral immune evasion, neoan-giogenesis, extracellular matrix remodeling and dysregulated tumor cell proliferation. Our prior studies revealed that macrophage-derived, but not tumor cell-derived, macrophage migration inhibitory factor (MIF), is an important determinant of TAM alternative activation and M2 polarization. Aim: Because MIF is historically thought to initiate signaling via a receptor-dependent, outside-in mode of action, we wished to investigate the specific contributions of tumor-derived vs. macrophage-derived MIF to M2 marker expression during macrophage polarization. Design: Murine oral squamous cell-carcinoma cells (SCCVII) were co-cultured with either the RAW 264.7 mouse macrophage cell line or mouse primary bone marrow-derived macrophages in the context of MIF genetic loss/inhibition individually or in combination each cell type. Methods: Twelve well Transwell plates were used to co-culture SCCVII cells and RAW 264.7, MIF+/+ or MIF-/- macrophages treated with/without the small molecule MIF inhibitor, 4-iodo-6-phenylpyrimidine and incubated in the presence or absence of interleukin (IL-4) for 48 h. Macrophages were analyzed by quantitative real-time polymerase chain reaction and/or immunoblotting for relative macrophage polarization marker expression. Results: IL-4 treatment synergizes with SCCVII co-culture in inducing the expression of macrophage M2 markers and loss or inhibition of macrophage-derived MIF significantly reduces both IL-4 alone and IL-4/SCCVII co-culture-induced macrophage M2 marker expression. Conclusion: These studies identify an important and dominant requirement for macrophage MIF in maximal Th2-cytokine and oral squamous carcinoma cell-induced macrophage polarization and M2 marker expression. (AU)

• FAPESP's process: 15/15170-4 - Study of the role of the Macrophage Migration Inhibitory Factor in the modulation of the tumor inflammatory infiltrate and progression of oral squamous cell carcinoma
• Grantee: Mariana Barbosa de Souza Rizzo
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 15/02584-5 - The role of the Macrophage Migration Inhibitory Factor in the modulation of the tumor inflammatory infiltrate and progression of oral squamous cell carcinoma
• Grantee: Mariana Barbosa de Souza Rizzo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/03453-1 - The role of cancer-associated inflammation in the regional dissemination of the oral squamous cell carcinoma
• Grantee: Marcos Brasilino de Carvalho
• Support Opportunities: Regular Research Grants