INICSA   23916
INSTITUTO DE INVESTIGACIONES EN CIENCIAS DE LA SALUD
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
EXTRACELLULAR VESICLES AS CARRIERS OF CD147 IN THYROID TUMOR MICROENVIRONMENT
Autor/es:
DE PAUL, ANA; REMEDI, MÓNICA; DONADÍO, ANA CAROLINA; BORIOLI, GRACIELA; MASINI DE REPISO, ANA MARÍA; BRAVO, ROCÍO; GILARDONI, MÓNICA; PELLIZAS, CLAUDIA
Lugar:
San Pablo
Reunión:
Congreso; XVI Latin American Thyroid Congress; 2017
Institución organizadora:
Asociación Latinoamericana de Tiroides
Resumen:
The influence of tumor-stromal crosstalk on tumor progression is recognized in different types of cancer. Tumor-secreted extracellular vesicles (EVs) act as intercellular messengers between tumor and stromal cells in local and distant microenvironments. The mechanisms by which tumor cells establish a permissive microenvironment that promotes thyroid cancer progression remain largely undefined.CD147 is a transmembrane glycoprotein that induces matrix metalloproteinases (MMPs) expression. CD147 level correlates with the dedifferentiation-degree of thyroid cancer and has also been suggested as a significant prognostic factor in differentiated thyroid carcinomas. In preliminary studies, we found that thyroid tumor cell-fibroblasts (Fb) interaction promotes the secretion and activation of MMPs and tumor cell migration.Objectives: To identify EVs production and their CD147 expression as potential features of thyroid tumor malignant progression in a model of tumor-stroma cell interaction.Methods: As an in vitro tumor-stroma cell interaction model, non-tumor cells (N-ThyOri), thyroid papillary carcinoma cells (TPC-1) and thyroid anaplastic cells (8505c) were co-cultured with normal Fb. EVs were isolated from conditioned media (CMs) by differential centrifugation and filtration steps. EVs ultrastructural features, and EVs sizes and populations in co-cultured and isolated cells were characterized by Transmission Electronic Microscopy (TEM) and Dynamic Light Scattering. CD147 expression was analyzed by western blotting and immunogold labeling in EVs, and by indirect immunofluorescence in whole cells.Results: Cell membrane periphery of thyroid cell-Fb co-cultures was rich in both round and villi-like membrane projections. In contrast, TEM analysis of normal Fb or isolated thyroid cells revealed a smoother cell surface. Isolated EVs from CMs ranged between 50-600nm. The CD147 protein in EVs from CMs evidenced a higher expression in TPC-1-Fb and 8505c-Fb co-cultures when compared to N-ThyOri-Fb co-cultures. By immunofluorescence, CD147 expression in whole tumor thyroid cells displayed a dotted pattern during thyroid tumor cell-Fb co-culture.Conclusion: The results suggest that CD147 could play an active role in intercellular communication events in thyroid-tumor microenvironment, stimulating the release of MMPs by cells in this environment and the consequent migration and cellular invasion.