Abstract
Exosomes are membrane-bound extracellular vesicles (EVs) released by most cells, having a size ranging from 30 to 150 nm, and are involved in mechanisms of cell-cell communication in physiological and pathological tissues. Exosomes are engaged in the transport of biomolecules, such as lipids, proteins, messenger RNAs, and microRNA, and in signal transmission through the intercellular transfer of components. In the context of proteins and nucleic acids transported from exosomes, our interest is focused on the Frizzled proteins family and related messenger RNA. Exosomes can regenerate stem cell phenotypes and convert them into cancer stem cells by regulating the Wnt pathway receptor family, namely Frizzled proteins. In particular, for gastrointestinal cancers, the Frizzled protein involved in those mechanisms is Frizzled-10 (FZD-10). Currently, increasing attention is being devoted to the protein and lipid composition of exosomes interior and membranes, representing profound knowledge of specific exosomes composition fundamental for their application as new delivering drug tools for cancer therapy. This review intends to cover the most recent literature on the use of exosome vesicles for early diagnosis, follow-up, and the use of these physiological nanovectors as drug delivery systems for gastrointestinal cancer therapy.
Highlights
In the last decade, a significant number of studies have focused their attention on the exosome-mediated cross talking that occurs between cancer and normal cells, especially in the tumor microenvironment, which is able to promote the activation of signaling pathways and, reprogram the functions of recipient cells by means of their cargo transfer [1]
The authors found that the macrophage migration inhibitory factor (MIF) is highly expressed in pancreatic ductal adenocarcinoma (PDAC)-derived exosomes, extracted from stage I PDAC patients, and that liver pre-metastatic niche formation and metastasis can be prevented by an MIF blockade. These results indicated that MIF delivered by PDAC-derived exosomes may represent a valid prognostic marker for the development of PDAC liver metastasis [27]
In a very recent study, we investigated the specific role in carcinogenesis of both FZD10, a protein directly involved in carcinogenesis and tumor proliferation, and its messenger RNA (FZD10-mRNA), which have been demonstrated to be carried by exosomes isolated from different gastrointestinal cancer cells, namely human colorectal adenocarcinoma cells (CaCo-2), metastatic SW-620 colon cancer cells, hepatocellular carcinoma cell lines (Hep-3B, HLF, and HLE cells), liver hepatoma cells (PLC-5), gastric carcinoma cells, human gastric carcinoma cells, and human intrahepatic cholangiocellular carcinoma cells (HUCCT-1)
Summary
A significant number of studies have focused their attention on the exosome-mediated cross talking that occurs between cancer and normal cells, especially in the tumor microenvironment, which is able to promote the activation of signaling pathways and, reprogram the functions of recipient cells by means of their cargo transfer [1]. Exosome cargo includes mRNA, DNA, microRNA (miRNA), and long noncoding RNA (LncRNA) that can induce genetic and epigenetic modifications in recipient cells in terms of activity and functions [13] Lipids, such as cholesterol, phospholipids, glycerophospholipids, sphingolipids, and ceramides, are essential components of exosomes as they form a much more stable bilayer membrane structure [14]. The potential of exosomes as drug delivery nanocarriers for the treatment of gastrointestinal cancers will be discussed, envisioning a future effective therapeutic alternative with respect to conventional disease management
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