BackgroundCancer-associated fibroblasts (CAFs) are functionally and structurally essential for tumor progression. There are 3 main origins of CAFs: mesenchymal stem cells (MSCs), epithelial-to-mesenchymal (EMT) transition cells, and tissue-resident cells. Pericytes retain characteristics of progenitor cells and can differentiate into other cells under normal physiological conditions and into myofibroblasts under pathological conditions. Exosomes play an important role in intercellular communication by transferring membrane components and nucleic acids between different cells. In this study, we evaluated whether cancer cell-derived exosomes are involved in regulating the transition of pericytes to CAFs.Material/MethodsExosomes from GES-1 and SGC7901 cells were isolated by serial centrifugation and purified from the supernatant by the 30% sucrose/D2O cushion method. A transmission electron microscope was used to observe exosome morphologies, and nanoparticle tracking analysis was used to analyze size distribution of exosomes. Western blot analysis, immunofluorescent staining, and qPCR were employed to detect CAFs marker expression and signaling pathways involved in CAFs transition.ResultsGastric cancer cell-derived exosomes enhanced pericytes proliferation and migration and induced the expression of CAFs marker in pericytes. We then demonstrated that the PI3K/AKT and MEK/ERK pathways were activated by tumor-derived exosomes, and BMP pathway inhibition reverses cancer exosomes-induced CAFs transition.ConclusionsOur results suggest that gastric cancer cells induce the transition of pericytes to CAFs by exosomes-mediated BMP transfer and PI3K/AKT and MEK/ERK pathway activation, and suggest that pericytes may be an important source of CAFs.
Colon cancer is one of the most common cancers in the world. Epithelial-to-mesenchymal transition (EMT) is a crucial step in tumor progression and also involves in the acquisition of stem cell-like properties. Some miRNAs have been shown to function as either tumor suppressors or oncogenes in colon cancer. Here, we investigated the role of miR-147 in the regulation of stem cell-like traits of colon cancer cells. We observed that miR-147 was down-regulated in several colon cancer cell lines and overexpressed miR-147 decreased the expression of cancer stem cell (CSC) markers OCT4, SOX2 and NANOG in colon cancer cells (HCT116, SW480). Besides that, overexpressed miR-147 inhibited EMT by increasing the expression of epithelial markers Ecadherin and α-catenin while decreasing the expression of mesenchymal markers fibronectin and vimentin. Moreover, activation of EMT by TGF-β1 treatment counteracted the inhibitive effect of miR-147 on the expression of CSC markers OCT4, SOX2 and NANOG significantly, supporting that overexpressed miR-147 inhibited stem cell-like traits by suppressing EMT in colon cancer. In addition, we found that overexpressed miR-147 down-regulated the expression of β-Catenin, c-myc and Survivin which were related to Wnt/β-Catenin pathway. Moreover, treatment with Wnt/β-Catenin pathway activator Licl in miR-147 mimic transfected cells attenuated the inhibitive effect of miR-147 mimic on EMT and stem cell-like traits of colon cancer cells, indicating that ectopic expression of miR-147 inhibited stem cell-like traits in colon cancer cells through suppressing EMT via the Wnt/β-Catenin pathway. In summary, our present study highlighted the crucial role of miR-147 in the inhibition of stem cell-like traits of colon cancer cells and indicated that miR-147 could be a promising therapeutic target for colon cancer treatment.
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