Effect of Interferon-γon the Basal and the TNFα-Stimulated Secretion of CXCL8 in Thyroid Cancer Cell Lines Bearing Either the RET/PTC Rearrangement Or the BRAF V600e Mutation
CXCL8 displays several tumor-promoting effects. Targeting and/or lowering CXCL8 concentrations within the tumor microenvironment would produce a therapeutic benefit. Aim of this study was to test the effect of IFNγon the basal and TNFα-stimulated secretion of CXCL8 in TCP-1 and BCPAP thyroid cancer cell lines (harboring RET/PTC rearrangement and BRAF V600e mutation, resp.). Cells were incubated with IFNγ(1, 10, 100, and 1000 U/mL) alone or in combination with TNF-α(10 ng/mL) for 24 hours. CXCL8 and CXCL10 concentrations were measured in the cell supernatants. IFNγinhibited in a dose-dependent and significant manner both the basal (ANOVAF: 22.759;p<0.00001) and the TNFα-stimulated (ANOVAF: 15.309;p<0.00001) CXCL8 secretions in BCPAP but not in TPC-1 cells (NS). On the other hand, IFNγand IFNγ+ TNF-αinduced a significant secretion of CXCL10 in both BCPAP (p<0.05) and TPC-1 (p<0.05) cells. Transwell migration assay showed that (i) CXCL8 increased cell migration in both TPC-1 and BCPAP cells; (ii) IFNγsignificantly reduced the migration only of BCPAP cells; and (iii) CXCL8 reverted the effect of IFNγ. These results constitute the first demonstration that IFNγinhibits CXCL8 secretion and in turn the migration of a BRAF V600e mutated thyroid cell line.