Extracellular vesicles induce fibroblasts metalloproteinases expression in thyroid tumor microenvironment

Barcelona

Encuentro; International Society for Extracellular Vesicles Annual Meeting; 2018

International Society for Extracellular Vesicles

The tumor microenvironment (TME), conformed by cellular and non-cellular components, promotes tumorigenesis in many solid malignancies. Extracellularvesicles (EVs) are related with intercellular communication in the TME.Fibroblasts (Fb), present in the TME, foster tumor growth stimulating cellproliferation and secreting extracellular matrix-remodelling proteases such asmatrix metalloproteinases (MMPs). CD147, a glycoprotein implicated in MMPsexpression, is related to thyroid tumor progression. Previous studies showedthat thyroid tumor cell-Fb interactions promoted the secretion of MMPs to culture supernatants (CMs) and a migratory phenotype in tumor cells. Our goalwas to identify EVs production and their role as mediators of MMPs expressionin 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 andcell-Fb CMs, were characterised by Transmission Electronic Microscopy andDynamic Light Scattering. MMPs were studied by zymography in EVs and CMsof 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, anincrease in MMP9 and active MMP2 was observed in Fb treated with EVscollected from tumor cell-Fb cocultures. Equally, an increased MMP2 andMMP9 expression was previously detected by immunocytochemistry in Fbcocultured with thyroid tumor cells. CD147 expression was detected in EVs andsignificantly increased in TPC-1-Fb and 8505c-Fb cocultures, without changesin NThyOri-Fb cocultures.The results suggest that EVs play an active role in intercellular communicationevents in thyroid TME, stimulating the Fb release of MMPs and the consequenttumor cell migration.