Abstract
Exosomes belong to the family of extracellular vesicles released by every type of cell both in normal and pathological conditions. Growing interest in studies indicates that extracellular vesicles, in particular, the fraction named exosomes containing lipids, proteins and nucleic acid, represent an efficient way to transfer functional cargoes between cells, thus combining all the other cell–cell interaction mechanisms known so far. Only a few decades ago, the involvement of exosomes in the carcinogenesis in different tissues was discovered, and very recently it was also observed how they carry and modulate the presence of Wnt pathway proteins, involved in the carcinogenesis of gastrointestinal 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 neoplastic features in normal cells. Exosomes derived from two different colon cancer cell lines, namely the non-metastatic CaCo-2 and the metastatic SW620, were found to deliver, in both cases, FZD10, thus demonstrating the ability to reprogram normal colonic epithelial cell line (HCEC-1CT). Indeed, the acquisition of specific mesenchymal characteristics, such as migration capability and expression of FZD10 and markers of mesenchymal cells, was observed. The exosomes derived from the metastatic cell line, characterized by a level of FZD10 higher than the exosomes extracted from the non-metastatic cells, were also more efficient in stimulating EMT activation. The overall results suggest that FZD10, delivered by circulating tumor-derived exosomes, can play a relevant role in promoting the CRC carcinogenesis and propagation.
Highlights
Extracellular vesicles (EVs) are biological lipid-bilayer delimited particles secreted by every type of cells into the extracellular space
Exosomes extracted from the culture medium of the untreated HCEC-1CT, SW620 and CaCo-2 cells were characterized in terms of morphology, size, size distribution and surface charge by Transmission Electron Microscopy (TEM), Int
Generally all EVs, may act as vectors for delivery of specific biological information and as mediators of intercellular signaling within multicellular organisms in both health and pathological conditions
Summary
Extracellular vesicles (EVs) are biological lipid-bilayer delimited particles secreted by every type of cells into the extracellular space. Exosomes secreted by breast and ovarian cancer cells resulted able to convey the specific physical and functional features of tumor-supporting myofibroblasts to adipose tissue-derived mesenchymal stem cells [8] Different proteins, such as vimentin, E-cadherin, N-cadherin, β-catenin and Slug/Snail, were found to be either upregulated or downregulated during the carcinogenesis, in particular during type 3 epithelial–mesenchymal transition (EMT), which is the process that converts epithelial cells into mesenchymal cells. On the basis of these premises, this study investigated the possible role of FZD10 delivering exosomes, derived either from metastatic and non-metastatic CRC cell lines, to act as messengers able to trigger reprogramming of normal colon epithelial cells To assess such a function of the FZD10 delivering exosomes, the acquisition of MCS-like features such as migration ability and expression of specific EMT involved proteins was evaluated
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