EXTRACELLULAR VESICLES: ANOTHER PIECE OF THE PUZZLE IN THYROID CANCER

DONADIO ANA CAROLINA

Mar del Plata

Simposio; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

Sociedad Argentina de Investigación Clínica

Medicina, Vol 82, Supl. V, p.30, 2022. Thyroid cancer (TC) is the most prevalent malignant disease of the endocrine system. Although most patients with TC have an excellent prognosis, around 30% of cases evolve in an unfavorable way. From the first stages of tumor initiation, malignant cells interact with different populations of non-cancer cells and the extracellular matrix (ECM) in the tumor microenvironment (TME). Theseinteractions include cell-to-cell contact, growth factor and cytokine signaling, and extracellular vesicles (EVs) exchanging bioactive molecules. Before their release, EVs are packed with bioactive molecules, including proteins, lipids, and nucleic acids. Importantly, interactions of EVs with recipient cells may regulate their pathophysiological state.The relevance of TME in TC is beginning to be clarified. In this sense, collagen deposition, ECM remodeling, and the concurrent presence of cancer activated fibroblasts have been described in association with more aggressive clinicopathological features. ECM remodeling creates a cancer permissive microenvironment andmatrix metalloproteinases (MMPs) are among the main drivers of ECM degradation. Using a simulation of thyroid TME, based on the co-culture of TPC-1 cells, from Papillary TC; 8505c, from Anaplastic TC; or NThyOri, as thyroid non-tumor cells with human fibroblasts (Fb), we described that thyroid tumor cell-Fb interplay provides a permissive environment for the expression of MMP2 andMMP9 enzymes, also increasing the migratory phenotype of thyroid tumor cells. EVs, which express the classical exosome markers, are secreted from isolated and co-cultured cells. The over-representation analysis of enriched proteins from Fb-TPC-1-and Fb-8505c compared with Fb-NThyOri-derived EVs showed functional convergence in ECM remodeling. Moreover, only those vesicles derived from tumor cell-Fb interacting cells were able to modify the proteolytic performance of Fb, increasing the expression of MMP2. Uptake studies demonstrated a higher avidity of Fb to incorporate EVs from tumoral thyroid context, providing more efficient crosstalk between Fb and thyroid tumor cells. Interestingly, MMP2 interactors allow EVs from tumoral and non-tumoral contexts to be discriminated. The knowledge of the EV-cargo and a better the understanding of their biological function, could contribute to promoting novel treatment strategies,offering opportunities for minimally invasive procedures for the diagnosis and monitoring of cancer patients.