Multicellular spheroids from normal and neoplastic thyroid tissues as a suitable model to test the effects of multikinase inhibitors

Valentina Cirello, Valentina Vaira, Elisa Stellaria Grassi, Valeria Vezzoli, Dario Ricca, Carla Colombo, Silvano Bosari, Leonardo Vicentini, Luca Persani, Stefano Ferrero, Laura Fugazzola

Research output: Contribution to journalArticle

Abstract

Multicellular three-dimensional (3D) spheroids represent an experimental model that is intermediate in its complexity between monolayer cultures and patients' tumor. In the present study, we characterize multicellular spheroids from papillary (PTC) and follicular (FTC) thyroid cancers and from the corresponding normal tissues. We show that these 3D structures well recapitulate the features of the original tissues, in either the differentiated and "stem-like" components. As a second step, we were aimed to test the effects of a small multikinase inhibitor, SP600125 (SP), previously shown to efficiently induce cell death in undifferentiated thyroid cancer monolayer cultures. We demonstrate the potent effect of SP on cell growth and survival in our 3D multicellular cultures. SP exerts its main effects through direct and highly significant inhibition of the ROCK pathway, known to be involved in the regulation of cell migration and β-catenin turnover. Consistently, SP treatment resulted in a significant decrease in β-catenin levels with respect to basal conditions in tumor but not in normal spheroids, indicating that the effect is promisingly selective on tumor cells.In conclusion, we provide the morphological and molecular characterization of thyroid normal and tumor spheroids. In this 3D model we tested in vitro the effects of the multikinase inhibitor SP and further characterized its mechanism of action in both normal and tumor spheroids, thus making it an ideal candidate for developing new drugs against thyroid cancer.

Original languageEnglish
Pages (from-to)9752-9766
Number of pages15
JournalOncotarget
Volume8
Issue number6
DOIs
Publication statusPublished - Feb 7 2017

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Cellular Spheroids
Thyroid Gland
Catenins
Neoplasms
Thyroid Neoplasms
Factor IX
Cell Movement
Cell Survival
Cell Death
Theoretical Models
anthra(1,9-cd)pyrazol-6(2H)-one
Growth
Pharmaceutical Preparations

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  • Journal Article

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Multicellular spheroids from normal and neoplastic thyroid tissues as a suitable model to test the effects of multikinase inhibitors. / Cirello, Valentina; Vaira, Valentina; Grassi, Elisa Stellaria; Vezzoli, Valeria; Ricca, Dario; Colombo, Carla; Bosari, Silvano; Vicentini, Leonardo; Persani, Luca; Ferrero, Stefano; Fugazzola, Laura.

In: Oncotarget, Vol. 8, No. 6, 07.02.2017, p. 9752-9766.

Research output: Contribution to journalArticle

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AU - Grassi, Elisa Stellaria

AU - Vezzoli, Valeria

AU - Ricca, Dario

AU - Colombo, Carla

AU - Bosari, Silvano

AU - Vicentini, Leonardo

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AU - Ferrero, Stefano

AU - Fugazzola, Laura

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