EXPLORING NANOMETER UNIVERSES TO DECIPHER THE EMISSARIES OF THE TUMOR

ROYO, FÉLIX; DONADIO, ANA CAROLINA; CESCHIN, DANILO GUILLERMO; JUAN MANUEL, FALCÓN-PEREZ; BRAVO-MIANA, ROCÍO DEL CARMEN; PELLIZAS, CLAUDIA GABRIELA

Virtual

Congreso; Reunión de Sociedades de Biociencias 2021; 2021

SAIC, SAI, AAFE, NANOMED-AR

Extracellular vesicles (EVs) participate in tumor-stroma crosstalk within the tumor microenvironment (TME) contributing to tumor promotion. Thyroid cancer is the most prevalent endocrine malignancy, and the relevance of fibroblasts (Fb) and EVs in the TME is beginning to be elucidated. Using an in vitro model, we demonstrated that Fb-thyroid tumor cell co-culture induced the activity of matrix metalloproteinase-2 (MMP2), and that the EVs obtained from these cultures stimulated the secretion and activation of MMP2 by normal Fb. Given this background, we hypothesized that the interaction of thyroid tumor cells with Fb would promote modifications in the EVs? protein cargo, which would influence their communication with the TME components. Besides, EVs would enable the study of potential biomarkers for the diagnosis and monitoring of the evolution in cancer patients. The bioinformatic analysis of EV-proteomic data identified 1977 proteins; 98% of EV-protein cargo and 97 out of 100- most frequent proteins in Vesiclepedia database were identified in our samples, thus confirming the identity and purity of the EVs samplesanalyzed. Furthermore, we demonstrated that EVs released from Fb-thyroid tumor cell co-culture expressed a proteomic profile related with extracellular matrix (ECM) remodeling. Specifically, thecrosstalk between Fb and a papillary thyroid cancer cell line (TPC-1) enhanced the functionality of EVs for collagen degradation. Consistently, MMP2 and its related proteins, detected in EVs, allowed to discriminate between EVs from tumoral and non-tumoral contexts.Finally, the proteins HRAS and MAMDC2 that were found to be enriched in EVs from Fb-TPC-1 co-culture, constitute interesting targets for further studies as cancer biomarkers. In conclusion, EVsproduced in the thyroid tumor milieu participate in ECM remodeling, promoting the synthesis and local activation of MMPs, facilitating ECM-degradation as well as tumor aggressiveness and progression.