TY - JOUR
T1 - Dysregulation of secretion of CXC α-chemokine CXCL10 in papillary thyroid cancer
T2 - Modulation by peroxisome proliferator-activated receptor-γ agonists
AU - Antonelli, Alessandro
AU - Ferrari, Silvia Martina
AU - Fallahi, Poupak
AU - Frascerra, Silvia
AU - Piaggi, Simona
AU - Gelmini, Stefania
AU - Lupi, Cristiana
AU - Minuto, Michele
AU - Berti, Piero
AU - Benvenga, Salvatore
AU - Basolo, Fulvio
AU - Orlando, Claudio
AU - Miccoli, Paolo
PY - 2009/12
Y1 - 2009/12
N2 - In papillary thyroid carcinomas (PTCs), oncogenes activate a transcriptional program including the upregulation of CXCL10 chemokine, which stimulates proliferation and invasion. Furthermore, peroxisome proliferator-activated receptor-γ (PPARγ) activators thiazolidinediones (TZDs) modulate CXCL10 secretion in normal thyroid follicular cells (TFC), and inhibit PTC growth. Until now, no study has evaluated the effect of cytokines on CXCL10 secretion in PTCs, nor the effect of PPARγ activation. The combined effects of interferon γ (IFNγ) and tumor necrosis factor α (TNFα) stimulation on CXCL10 secretion in primary cells from PTCs and TFC were tested. Furthermore, the effect of PPARγ activation by TZDs, on CXCL10 secretion and proliferation in these cell types was studied. In primary cultures of TFC and PTCs CXCL10 production was absent under basal conditions; a similar dose-dependent secretion of CXCL10 was induced by IFNγ in both cell types. TNFα alone induced a slight but significant CXCL10 secretion only in PTCs. The stimulation with IFNγ+TNFα induced a synergistic CXCL10 release in both cell types; however, a secretion more than ten times higher was induced in PTCs. Treatment of TFC with TZDs dose-dependently suppressed IFNγ+TNFα-induced CXCL10 release, while TZDs stimulated CXCL10 secretion in PTCs. A significant antiproliferative effect by TZDs was observed only in PTCs. In conclusion, a dysregulation of CXCL10 secretion has been shown in PTCs. In fact, a CXCL10 secretion more than ten times higher has been induced by IFNγ+TNFα in PTCs with respect to TFC. Moreover, TZDs inhibited CXCL10 secretion in TFC and stimulated it in PTCs. The effect of TZDs on CXCL10 was unrelated to the significant antiproliferative effect in PTCs.
AB - In papillary thyroid carcinomas (PTCs), oncogenes activate a transcriptional program including the upregulation of CXCL10 chemokine, which stimulates proliferation and invasion. Furthermore, peroxisome proliferator-activated receptor-γ (PPARγ) activators thiazolidinediones (TZDs) modulate CXCL10 secretion in normal thyroid follicular cells (TFC), and inhibit PTC growth. Until now, no study has evaluated the effect of cytokines on CXCL10 secretion in PTCs, nor the effect of PPARγ activation. The combined effects of interferon γ (IFNγ) and tumor necrosis factor α (TNFα) stimulation on CXCL10 secretion in primary cells from PTCs and TFC were tested. Furthermore, the effect of PPARγ activation by TZDs, on CXCL10 secretion and proliferation in these cell types was studied. In primary cultures of TFC and PTCs CXCL10 production was absent under basal conditions; a similar dose-dependent secretion of CXCL10 was induced by IFNγ in both cell types. TNFα alone induced a slight but significant CXCL10 secretion only in PTCs. The stimulation with IFNγ+TNFα induced a synergistic CXCL10 release in both cell types; however, a secretion more than ten times higher was induced in PTCs. Treatment of TFC with TZDs dose-dependently suppressed IFNγ+TNFα-induced CXCL10 release, while TZDs stimulated CXCL10 secretion in PTCs. A significant antiproliferative effect by TZDs was observed only in PTCs. In conclusion, a dysregulation of CXCL10 secretion has been shown in PTCs. In fact, a CXCL10 secretion more than ten times higher has been induced by IFNγ+TNFα in PTCs with respect to TFC. Moreover, TZDs inhibited CXCL10 secretion in TFC and stimulated it in PTCs. The effect of TZDs on CXCL10 was unrelated to the significant antiproliferative effect in PTCs.
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U2 - 10.1677/ERC-08-0337
DO - 10.1677/ERC-08-0337
M3 - Article
C2 - 19755523
AN - SCOPUS:72549106749
VL - 16
SP - 1299
EP - 1311
JO - Endocrine-Related Cancer
JF - Endocrine-Related Cancer
SN - 1351-0088
IS - 4
ER -