Biophysical and biomolecular analysis of EVs and their interaction with target cells

Triple negative breast cancer (TNBC) is one of the most aggressive breast cancer subtype and with a poor prognosis. Nowadays, chemotherapy is the main treatment in both early and advanced stage of the TNBC, but patients without complete response to conventional chemotherapy are approximately 80%. In light of that, clarifying biological mechanisms of the metastatic process is crucial in finding new therapeutic approaches for effective interventions. Metastasis is thought to be easier for more deformable and, therefore, soft cancer cells, which can migrate through narrow pores of extracellular matrix and vessels. Extracellular vesicles derived from triple-negative breast cancer, by sharing oncogenic molecules, have been shown to promote proliferation, drug resistance migration and metastatic capability in target cells proportional to properties of donor ones. Considering all these evidence, we wondered if small-EVs could also transfer information to target cells about biomechanical properties, a key step in metastasis, of the cell from which they originate. Our results showed that small-EVs derived from the MDA-MB-231 cell line (TNBC) can directly modulate biomechanical properties (stiffness/Young’s modulus), cytoskeleton, nuclear morphology and Yap activity of MCF7 cell line (Luminal A) as target cell. Therefore, in this study, we found out a new mechanism through which small-EVs derived from TNBC subtype could be able to contribute to progression and metastatic processes in breast cancer; this new knowledge could be used in diagnostic and therapeutic field.