title: 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.
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.
authors.affiliation: 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.
authors.forename: Mario
authors.initials: M
authors.lastname: Rotondi
authors.affiliation: 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.
authors.forename: Francesca
authors.initials: F
authors.lastname: Coperchini
authors.affiliation: 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.
authors.forename: Oriana
authors.initials: O
authors.lastname: Awwad
authors.affiliation: Allergy and Immunology Unit, Fondazione Salvatore Maugeri I.R.C.C.S., 27100 Pavia, Italy.
authors.forename: Patrizia
authors.identifier: 0000-0001-5283-3897
authors.initials: P
authors.lastname: Pignatti
authors.affiliation: 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.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Di Buduo
authors.affiliation: 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.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Abbonante
authors.affiliation: 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.
authors.forename: Flavia
authors.initials: F
authors.lastname: Magri
authors.affiliation: 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.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Balduini
authors.affiliation: 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.
authors.forename: Luca
authors.identifier: 0000-0001-7457-7353
authors.initials: L
authors.lastname: Chiovato
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D054357:Chemokine CXCL10 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism*; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014945:Wound Healing
chemical_list: C114753:CXCL10 protein, human; C508606:CXCL8 protein, human; D054357:Chemokine CXCL10; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf