Thyroid cancer is the most common endocrine cancer with predominant prevalence of papillary thyroid cancer (PTC) histotype, that frequently presents with epithelial-mesenchimal transition through which cells express mesenchymal markers associated with metastases and aggressive behavior. This process, called epithelial to mesenchymal transition (EMT) is characterized by the loss of epithelial markers and the acquisition of mesenchymal ones such as vimetin, desmin and others. Genetic and epigenetic alterations originated in the tumor stroma are responsible of these changes. Hypoxic conditions and many molecules such as HMGB1, HGF, EGF, PDGF and TGF beta have been identified as inducers of the EMT process in thyroid cancer. MiRNAs play an important role in thyroid cancer and the overexpression of miR221, 222 and many others is associated with tumor progression.
One way through which cells communicate and transfer information to one another in solid tumors or between tumor and microenvironment is through the release of vesicles (EV) that contain proteins and nucleic acids able to deliver both inhibitory and stimulating messages. Small non coding RNAs that are known regulators of protein expression, found in microvesicles, are implicated in most cell processes from survival, proliferation and acquisition of stem cell markers. The opposite process i.e mesenchymal-epithelial transition (MET) in which mesenchymal cells are converted into epithelial cells is still poorly understood, and much more work needs to be done to gain a firm grasp of how it works. This project aims to study the mechanisms that may induce EMT in papillary tumor cell lines (BC PAP) and the reverse transition (MET) from stemness to differentiation in thyroid cancer cell lines. Among the EMT promoters miR 9, 200 a and 200c have been shown to play a role in thyroid cancer progression while inhibitory microRNAs such as miR599 and 520a repress EMT by down regulation of activating signaling pathways.
