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Mediators Inflamm. 2016;2016:8512417. doi: 10.1155/2016/8512417. Epub 2016 Jul 31.

Effect of Interferon-γ on 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.

Author information

1
Unit of Internal Medicine and Endocrinology, Fondazione Salvatore Maugeri I.R.C.C.S., Laboratory for Endocrine Disruptors and Chair of Endocrinology University of Pavia, 27100 Pavia, Italy.
2
Unit of Internal Medicine and Endocrinology, Fondazione Salvatore Maugeri I.R.C.C.S., Laboratory for Endocrine Disruptors and Chair of Endocrinology University of Pavia, 27100 Pavia, Italy; Department of Biopharmaceutics and Clinical Pharmacy, The University of Jordan, Amman 11937, Jordan.
3
Allergy and Immunology Unit, Fondazione Salvatore Maugeri I.R.C.C.S., 27100 Pavia, Italy.
4
Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy; Biotechnology Research Laboratories, I.R.C.C.S., Policlinico San Matteo Foundation, 27100 Pavia, Italy.
5
Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy; Biotechnology Research Laboratories, I.R.C.C.S., Policlinico San Matteo Foundation, 27100 Pavia, Italy; Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.

Abstract

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 IFNγ on 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. IFNγ inhibited in a dose-dependent and significant manner both the basal (ANOVA F: 22.759; p < 0.00001) and the TNFα-stimulated (ANOVA F: 15.309; p < 0.00001) CXCL8 secretions in BCPAP but not in TPC-1 cells (NS). On the other hand, IFNγ and IFNγ + TNF-α induced 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) IFNγ significantly reduced the migration only of BCPAP cells; and (iii) CXCL8 reverted the effect of IFNγ. These results constitute the first demonstration that IFNγ inhibits CXCL8 secretion and in turn the migration of a BRAF V600e mutated thyroid cell line.

PMID:
27555670
PMCID:
PMC4983361
DOI:
10.1155/2016/8512417
[Indexed for MEDLINE]
Free PMC Article

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