We tested in "primary human anaplastic thyroid carcinoma (ATC) cells" (ANA) versus "normal thyroid follicular cells" (TFC): a) CCL2 secretion basally, after IFN-γ and/or TNF-α stimulation; b) PPARγ activation by thiazolidinediones (TZDs), rosiglitazone or pioglitazone, on CCL2 secretion, and on proliferation and apoptosis in ANA.
We recently reported that peroxisome proliferator-activated receptor gamma (PPARγ) is highly expressed in ATC and confers an aggressive phenotype when overexpressed in DTC cells.
Redifferentiation and induction of tumor suppressors miR-122 and miR-375 by the PAX8/PPARγ fusion protein inhibits anaplastic thyroid cancer: a novel therapeutic strategy.
We further implicate RhoB as a key signaling effector for the growth inhibition of ATC, as treatment with a histone deacetylase inhibitor shown to increase RhoB expression in lung cancer cells caused the up-regulation of RhoB in ATC cells accompanied by increased expression of p21 and inhibition of cell proliferation; this effect occurred even in ATC cells that were unresponsive to RS5444 due to a lack of expression of PPARgamma.
In contrast, genetic alterations in follicular carcinomas include PAX8-PPARgamma translocations and RAS mutations while mutations of CTNNB1 and p53 have been implicated in the development and progression of poorly differentiated and undifferentiated (anaplastic) thyroid carcinomas.
Our results indicated that PPARgamma ligands modify malignant potential of anaplastic carcinoma cell lines altering growth or invasive properties, suggesting that PPARgamma could be potentially the novel molecular target for human thyroid anaplastic carcinoma.