EXTRACELLULAR VESICLES AS CARRIERS OF CD147 IN THYROID TUMOR MICROENVIRONMENT

Rio de Janeiro

Congreso; XVI Latin American Thyroid Congress; 2017

Latin American Thyroid Society

Tumors are composed of two discrete but interactive compartments, the tumor cells themselves orparenchyma, and the stroma. Tumor stroma is conformed by endothelial cells, pericytes, invadinginflammatory cells, fibroblasts (Fb) and extracellular matrix (ECM) components. It is known thatbidirectional communication between tumor cells and the associated stroma represent a powerfulrelationship that influences disease initiation, progression and patient prognosis (Quail & Joyce, NatMed 19:1423, 2013).Matrix metalloproteinases (MMPs), a large family of zinc-dependent ECM-degrading endopeptidases,are proteolytic enzymes implicated in tumor-stroma crosstalk. CD147, a transmembraneglycoprotein highly expressed in many malignant tumor cells, is actively involved in the secretion andactivation of MMPs. In thyroid cancer, CD147 level correlates with the dedifferentiation-degree, andhas also been suggested as a significant prognostic factor in differentiated thyroid carcinomas (Tan etal., Transl Res 152:143, 2008; Huang et al., Int J Clin Exp Pathol 8:309, 2015).While soluble factors such as cytokines, enzymes and growth factors have been considered the mainmediators in intercelular communication, it is now recognized that eukaryotic cells also releasecomplex structures called extracellular vesicles (EVs), which contain proteins, lipids, and evennucleic acids, acting as intercellular messengers in local and distant microenvironments in much morecomplex ways (Becker et al., Cancer Cell 30, 836, 2016).Cancer-associated Fb are essential for tumor progression providing, both a functional and a structuralsupportive environment. In an experimental model of progressive Thyroid Papillary Carcinoma, Jollyand coworkers (Cancer Res. 76:1804, 2016) describe Fb recruitment, collagen I deposition and ECMremodeling as key elements in thyroid tumor progression. However, the role of thyroid tumor cell-Fbinteraction on EVs secretion, and on the modulation of proteins related with tumor invasion anddissemination, remains unknown.In preliminary studies, we found that thyroid tumor cell-Fb interaction promotes the secretion andactivation of MMP2. In addition, soluble factors present in Fb or Fb-thyroid tumor cells co-cultureincrease the percentage of thyroid tumor cells with migratory phenotype, evidenced by the presenceof filopodia and/or lamellipodia, an event that was not observed in non-tumoral thyroid cells