Frontiers in Endocrinology (May 2015)

IGF-1 influences Everolimus activity in medullary thyroid carcinoma

  • Erica eGentilin,
  • Erica eGentilin,
  • Carmelina eDi Pasquale,
  • Martina eRossi,
  • Federico eTagliati,
  • Teresa eGagliano,
  • Roberta eRossi,
  • Mariarosa ePelizzo,
  • Isabella eMerante Boschin,
  • Ettore C degli Uberti,
  • Ettore C degli Uberti,
  • Maria Chiara eZatelli,
  • Maria Chiara eZatelli

DOI
https://doi.org/10.3389/fendo.2015.00063
Journal volume & issue
Vol. 6

Abstract

Read online

Context: Medullary thyroid carcinoma (MTC) is a rare tumor originating from thyroid parafollicular C cells. It has been previously demonstrated that IGF-I protects MTC from the effects of anti-proliferative drugs. Everolimus, an mTOR inhibitor, has shown potent anti-proliferative effects in a human MTC cell line, TT, and in two human MTC primary culturesObjective: To verify whether IGF-I may influence the effects of Everolimus in a group of human MTC primary cultures.Design: We collected 18 MTCs that were dispersed in primary cultures, treated without or with 10 nM - 1 M Everolimus and/or 50 nM IGF-I. Cell viability was evaluated after 48 h and Calcitonin (CT) secretion was assessed after a 6 h incubation. IGF-I receptor downstream signalling protein expression profile was also investigated.Results: Everolimus significantly reduced cell viability in 8 MTC (by ~20%; P<0.01 vs. control; E-R MTCs), while cell viability did not change in 10 MTCs (E-NR MTCs). In E-R MTCs IGF-I blocked the antiproliferative effects of Everolimus, that did not affect CT secretion, but blocked the stimulatory effects of IGF-I on this parameter. IGF-I receptor downstream signalling proteins were expressed at higher levels in E-NR MTC as compared to E-R MTCs.Conclusions: IGF-I protects a sub-set of MTC primary cultures from the antiproliferative effects of Everolimus and stimulates CT secretion by an mTOR mediated pathway, that, in turn, may represent a therapeutic target in the treatment of aggressive MTCs.

Keywords