Targeting epidermal growth factor receptor 1 signaling in human thyroid-stimulating hormone-independent thyroid carcinoma FRO cells results in a more chemosensitive and less angiogenic phenotype.

Matteo Landriscina, Annamaria Piscazzi, Annarita Fabiano, Francesca Maddalena, Eleonora Costantino, Anna Farese, Pantaleo Bufo, Mauro Cignarelli

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Poorly differentiated and anaplastic thyroid cancers are aggressive malignancies unresponsive to standard treatments. The mechanisms responsible for the progression of thyroid tumors toward a thyroid-stimulating hormone (TSH)-independent phenotype are still under discussion, and a better understanding of them may provide novel molecular targets for the treatment of this disease. We evaluated the hypothesis that epithelial growth factor (EGF) signaling may play a role in favoring the loss of TSH dependency in human differentiated thyroid tumor cells. METHODS: The sensitivity to EGF stimulation was evaluated in follicular thyroid carcinoma WRO cells that retain some features of thyroid cell differentiation and in undifferentiated TSH-independent thyroid carcinoma FRO cells. RESULTS: It was observed that, while both cell lines are characterized by a similar EGF-dependent activation of the RAS/MAPK signaling pathway, only FRO cells exhibited a significant induction of phosphoAKT, cell proliferation, and migration as well as the up-regulation of vascular endothelial growth factor-A expression in response to EGF. On the other hand, the inhibition of epidermal growth factor receptor 1 signaling by its tyrosine kinase inhibitor, erlotinib, caused a selective down-regulation of FRO cell proliferation and induced a phenotype more sensitive to the proapoptotic activity of anthracyclins and taxoids. By contrast, the protracted stimulation of TSH-dependent WRO cells with EGF induced the loss of TSH dependency and the rearrangement of F-actin cytoskeleton. CONCLUSIONS: These results suggest that the acquired sensitivity to EGF in these thyroid tumor cells may be responsible for the loss of differentiation in the transition toward a TSH-independent, invasive, and chemoresistant phenotype.

Original languageEnglish
Pages (from-to)629-637
Number of pages9
JournalThyroid
Volume19
Issue number6
Publication statusPublished - Jun 2009

ASJC Scopus subject areas

  • Medicine(all)

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