ECE2020 Audio ePoster Presentations Thyroid (144 abstracts)
Octreotide and pasireotide effects on medullary thyroid carcinoma (MTC) cells growth, migration and invasion
Rosa Catalano 1,2 , Federica Mangili 1 , Elena Giardino 1 , Anna Maria Barbieri 1 , Donatella Treppiedi 1 , Alessia Dolci 3 , Andrea Contarino 3 , Anna Spada 1 , Maura Arosio 1,3 , Giovanna Mantovani 1,3 & Erika Peverelli 1
1University of Milan, Department of Clinical Sciences and Community Health, Milan, Italy; 2Sapienza University of Rome; 3Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor of the parafollicular thyroid C cells. Although somatostatin (SS) receptors (SSTs) are expressed by MTCs, treatment with octreotide, specific for SST2, has shown poor efficacy in reducing MTC proliferation, whereas pasireotide, a multi-receptor SS analogue with preferential binding to SST5, has recently demonstrated antiproliferative effects in persistent postoperative MTCs. In vitro data in human MTC cell line TT revealed differential responsiveness to antiproliferative and antisecretory effects of SST2 or SST5-selective agonists. Aim of this study was to test the effects of octreotide and pasireotide on MTC cells proliferation, cell cycle proteins expression, MAPK activation, apoptosis, calcitonin secretion, migration and invasion in TT cell line as well as in primary cultured cells obtained from sporadic or hereditary MTCs. Our results showed that both octreotide and pasireotide reduced TT cell proliferation (–41.7 ± 13.8%, P < 0.001 vs basal, and –31.3 ± 26%, P < 0.05 vs basal, respectively), with concomitant inhibition of ERK phosphorylation and cyclin D1 expression. This cytostatic effect was accompanied by a proapoptotic action, with an increase of caspase 3/7 activity of 1.4-fold with octreotide and 1.5-fold with pasireotide (both P < 0.001 vs basal). Moreover, both octreotide and pasireotide inhibited cell migration (-50.9 ± 11.3%, P < 0.01 vs basal, and –40.5 ± 17%, P < 0.05 vs basal, respectively, at 10–8 M) and invasion (-61.3 ± 35.1%, P < 0.05 vs basal, and –49.7 ± 18%, P < 0.01 vs basal, respectively, at 10–8 M). No effect was observed on calcitonin secretion after octreotide or pasireotide incubation. In primary cultured cells from MTC, octreotide and pasireotide were effective in reducing cyclin D1 expression in 1 out of 3 tumors, all expressing SST2 and SST5 at similar levels. Octreotide strongly reduced cell migration in 2 tumors tested, regardless of antiproliferative and antisecretory effects and RET mutational status. In conclusion, our data demonstrated a similar efficacy of octreotide and pasireotide in reducing cell growth and invasiveness in TT cells. In contrast,they exerted variable effects in MTC primary cultured cells, independently from the expression of SST2 and SST5, suggesting the need for new biomarkers useful to stratify patients for therapeutic response to SSAs.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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