The paramount role of cytokines and chemokines in papillary thyroid cancer: a review and experimental results
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Our study demonstrates that (C-X-C motif) ligand 9 and 11 (CXCL9, CXCL11) chemokines were absent basally in non-neoplastic thyroid (TFC) and papillary thyroid carcinoma (PTC) cells. Interferon (IFN)γ induced the chemokine secretion in TFC and PTC, while tumor necrosis factor (TNF)α induced it only in PTC. IFNγ+TNFα induced a synergistic chemokines release in PTC, and at a lower level in TFC. Peroxisome proliferator-activated receptor (PPAR)γ agonists suppressed dose-dependently IFNγ+TNFα-induced chemokine release in TFC, while stimulated it in PTC. PPARγ knocking down, by RNA interference technique in PTC cells, abolished the effect of PPARγ agonists on chemokines release. In PTC cells, PPARγ agonists reduced proliferation, and CXCL9 or CXCL11 (100 and 500 pg/mL) reduced proliferation and migration (P < 0.01, for all). In conclusion, in PTC cells: (a) IFNγ+TNFα induced a marked release of CXCL9 and CXCL11; (b) PPARγ agonists stimulated CXCL9 and CXCL11 secretion, while inhibited proliferation; (c) CXCL9 and CXCL11 inhibited proliferation and migration. The use of CXCL9 or CXCL11 as antineoplastic agents in PTC remains to be explored.
• IFNγ and IFNγ+TNFα induce dose-dependently CXCL9 (and less CXCL11) in PTC cells.
• Rosi and Pio dose-dependently inhibit the PTC cells proliferation.
• Rosi and Pio (at variance of normal TFC) stimulate CXCL9 or CXCL11 secretion.
• CXCL9 or CXCL11 induce a significant antiproliferative effect in PTC cells.
• Chemokines induced by IFNγ (CXCL9 or CXCL11) inhibit migration in PTC cells.
KeywordsCXCL9 CXCL11 Papillary thyroid cancer PPARγ CXCL10
We thank Dr. Michaela Francalanci for her contribution in the realization of siRNA studies.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Compliance with ethical standards
Conflict of Interests
The authors declare that they have no conflict of interest.
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