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

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.

Cancer chemoprevention through Frizzled receptors and EMT

“…This mechanism also functions in esophageal squamous cell carcinoma [ 108 ]. In colorectal cancer (CRC), cells with high FZD10 expression were more efficient than cells with low FZD10 at stimulating EMT [ 134 ]. In progression of CRC, FZD10 expression increases from non-dysplastic to dysplastic tissue, suggesting it is activated early in CRC development [ 102 ].…”

Exosome Released FZD10 Increases Ki-67 Expression via Phospho-ERK1/2 in Colorectal and Gastric Cancer

“…Evidence has been reported on a role of exosomes in the promotion of the EMT ( 38 – 41 ). In particular, FZD10-delivering exosomes were also indicated to trigger the EMT in a normal epithelial colon cell line, together with an increase of proteins, such as vimentin and c-Myc, shown to be overexpressed and involved in the mechanisms of cell migration, cell adhesion, and proliferation ( 27 ).…”

“…This has significant implications on cancer progression ( 25 ), and indeed, in the FZD10-mRNA-silenced cells, the viability was restored ( 26 ). We recently reported that activation of the epithelial–mesenchymal transition (EMT) in normal colon epithelial cells (HCEC-1CT) is triggered by FZD10-delivering exosomes extracted from CRC cell lines ( 27 ).…”

Therapeutic Potential of Exosomes in Pulmonary Fibrosis

“…Exosomes released from colon cancer cells with high levels of the Wnt receptor frizzled 10 protein (FZD10) can stimulate EMT activation to reprogram normal colonic epithelial cells (Scavo et al, 2020). Cancer stem cell-like cell-derived exosomal lncRNA DOCK9 antisense RNA2 (AS2) can activate the Wnt/β-catenin pathway to induce EMT and promote the progression of papillary thyroid carcinoma (Dai et al, 2020).…”