A Possible Role of FZD10 Delivering Exosomes Derived from Colon Cancers Cell Lines in Inducing Activation of Epithelial-Mesenchymal Transition in Normal Colon Epithelial Cell Line

Exosomes belong to the family of extracellular vesicles released by every type of cell both innormal and pathological conditions. Growing interest in studies indicates that extracellular vesicles,in particular, the fraction named exosomes containing lipids, proteins and nucleic acid, representan ecient way to transfer functional cargoes between cells, thus combining all the other cell-cellinteraction mechanisms known so far. Only a few decades ago, the involvement of exosomes inthe carcinogenesis in dierent tissues was discovered, and very recently it was also observed howthey carry and modulate the presence of Wnt pathway proteins, involved in the carcinogenesis ofgastrointestinal tissues, such as Frizzled 10 protein (FZD10), a membrane receptor for Wnt. Here,we report the in vitro study on the capability of tumor-derived exosomes to induce neoplasticfeatures in normal cells. Exosomes derived from two dierent colon cancer cell lines, namely thenon-metastatic CaCo-2 and the metastatic SW620, were found to deliver, in both cases, FZD10, thusdemonstrating the ability to reprogram normal colonic epithelial cell line (HCEC-1CT). Indeed, theacquisition of specific mesenchymal characteristics, such as migration capability and expression ofFZD10 and markers of mesenchymal cells, was observed. The exosomes derived from the metastaticcell line, characterized by a level of FZD10 higher than the exosomes extracted from the non-metastaticcells, were also more ecient in stimulating EMT activation. The overall results suggest that FZD10,delivered by circulating tumor-derived exosomes, can play a relevant role in promoting the CRCcarcinogenesis and propagation.