Ontology highlight
ABSTRACT: Background
Tumor-associated macrophages (TAMs) are important determinants of intratumoral immune evasion, neoangiogenesis, 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.
SUBMITTER: Barbosa de Souza Rizzo M
PROVIDER: S-EPMC6217709 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
Barbosa de Souza Rizzo M M Brasilino de Carvalho M M Kim E J EJ Rendon B E BE Noe J T JT Darlene Wise A A Mitchell R A RA
QJM : monthly journal of the Association of Physicians 20181101 11
<h4>Background</h4>Tumor-associated macrophages (TAMs) are important determinants of intratumoral immune evasion, neoangiogenesis, 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.<h4>Aim</h4>Because MIF is historically thought to initiate signaling via a receptor-depen ...[more]