ERC 5-year Impact Factor
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Endocrine-Related Cancer 16 (4) 1299 -1311     DOI: 10.1677/ERC-08-0337
Copyright © 2009 by the Society for Endocrinology
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
ERC-08-0337v1
16/4/1299    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Antonelli, A.
Right arrow Articles by Miccoli, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Antonelli, A.
Right arrow Articles by Miccoli, P.

Dysregulation of secretion of CXC {alpha}-chemokine CXCL10 in papillary thyroid cancer: modulation by peroxisome proliferator-activated receptor-{gamma} agonists

 Alessandro Antonelli1, Silvia Martina Ferrari1, Poupak Fallahi1, Silvia Frascerra1, Simona Piaggi3, Stefania Gelmini5, Cristiana Lupi4, Michele Minuto2, Piero Berti2, Salvatore Benvenga6, Fulvio Basolo4, Claudio Orlando5 and Paolo Miccoli2

1 Department of Internal Medicine
2 Department of Surgery
3 , Department of Experimental Pathology
4 Pathology Unit, School of Medicine, University of Pisa, Via Roma, 67, I-56100 Pisa, Italy
5 Clinical Biochemistry Unit, Department of Clinical Pathophysiology, University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy
6 Department of Endocrinology, University of Messina, Piazza Pugliatti, 1, 98122 Messina, Italy

(Correspondence should be addressed to A Antonelli; Email: a.antonelli{at}med.unipi.it)

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-{gamma} (PPAR{gamma}) 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 PPAR{gamma} activation. The combined effects of interferon {gamma} (IFN{gamma}) and tumor necrosis factor {alpha} (TNF{alpha}) stimulation on CXCL10 secretion in primary cells from PTCs and TFC were tested. Furthermore, the effect of PPAR{gamma} 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 IFN{gamma} in both cell types. TNF{alpha} alone induced a slight but significant CXCL10 secretion only in PTCs. The stimulation with IFN{gamma}+TNF{alpha} 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 IFN{gamma}+TNF{alpha}-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 IFN{gamma}+TNF{alpha} 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.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2009 by the Society for Endocrinology.