EXTRACELLULAR VESICLES INDUCE FIBROBLASTS METALLOPROTEINASES EXPRESSION IN THYROID TUMOR MICROENVIRONMENT

BRAVO MIANA, ROCÍO DEL CARMEN; DE PAUL, ANA LUCIA; DONADIO, ANA CAROLINA; GILARDONI, MONICA BEATRIZ; PELLIZAS, CLAUDIA GABRIELA; GUANTAY, MARIA LAURA; BORIOLI, GRACIELA ADRIANA

Barcelona

Congreso; International Society of Extracellular Vesicles Anual Meeting; 2018

International Society for Extracellular Vesicles

The tumor microenvironment (TME), conformed by cellular and non-cellular components, promotes tumorigenesis in many solid malignancies. Extracellular vesicles (EVs) are related with intercellular communication in the TME. Fibroblasts (Fb), present in the TME, foster tumor growth stimulating cell proliferation and secreting extracellular matrix-remodelling proteases such as matrix metalloproteinases (MMPs). CD147, a glycoprotein implicated in MMPs expression, is related to thyroid tumor progression. Previous studies showed that thyroid tumor cell-Fb interactions promoted the secretion of MMPs to culture supernatants (CMs) and a migratory phenotype in tumor cells. Our goal was to identify EVs production and their role as mediators of MMPs expression in thyroid TME. As an in vitro tumor-stroma cell interaction model, non-tumor cells (NThyOri), thyroid papillary carcinoma cells (TPC-1) and thyroid anaplastic cells (8505c) were cocultured with normal Fb. EVs, obtained by ultracentrifugation of cell and cell-Fb CMs, were characterised by Transmission Electronic Microscopy and Dynamic Light Scattering. MMPs were studied by zymography in EVs and CMs of Fb incubated with EVs. CD147 expression was analysed in EVs by gold-immunocytochemistry and Western blot. EVs ranged between 50-600nm. No MMPs activity was detected in EVs, but Fb incubated with EVs secreted MMP9 and MMP2 to CMs. Interestingly, an increase in MMP9 and active MMP2 was observed in Fb treated with EVs collected from tumor cell-Fb cocultures. Equally, an increased MMP2 and MMP9 expression was previously detected by immunocytochemistry in Fb cocultured with thyroid tumor cells. CD147 expression was detected in EVs and significantly increased in TPC-1-Fb and 8505c-Fb cocultures, without changes in NThyOri-Fb cocultures.The results suggest that EVs play an active role in intercellular communication events in thyroid TME, stimulating the Fb release of MMPs and the consequent tumor cell migration.