Abstract
Exosomes are nanoscale membrane vesicles secreted from many types of cells. Carrying functional molecules, exosomes transfer information between cells and mediate many physiological and pathological processes. In this report, utilizing selective inhibitors, molecular tools, and specific endocytosis markers, the cellular uptake of PC12 cell-derived exosomes was imaged by high-throughput microscopy and statistically analyzed. It was found that the uptake was through clathrin-mediated endocytosis and macropinocytosis. Furthermore, PC12 cell-derived exosomes can enter and deliver microRNAs (miRNAs) into bone marrow-derived mesenchymal stromal cells (BMSCs), and decrease the expression level of transforming growth factor β receptor II (TGFβRII) and tropomyosin-1 (TPM1) through miR-21. These results show the pathway of exosome internalization and demonstrate that tumor cell-derived exosomes regulate target gene expression in normal cells.
Highlights
Exosomes can transfer information between cells and facilitate tumor development
Using quantitative real-time PCR (RT-PCR) and immunoblot assay, it was demonstrated that PC12 cell-derived exosomes delivered miR-21 into bone marrow-derived mesenchymal stromal cells (BMSCs) and down-regulated the expression levels of their transforming growth factor  receptor II (TGFRII) and tropomyosin-1 (TPM1)
The suppression efficiencies for target genes of miR-21 may be cell type specific. These results indicated that PC12 cell-derived exosomes could decrease TGFRII and TPM1 in BMSCs through miR-21
Summary
Exosomes can transfer information between cells and facilitate tumor development. Results: PC12 cell-derived exosomes enter into BMSCs through clathrin-mediated endocytosis and macropinocytosis, and decrease the expression of TGFRII and TPM1 through miR-21. PC12 cell-derived exosomes can enter and deliver microRNAs (miRNAs) into bone marrow-derived mesenchymal stromal cells (BMSCs), and decrease the expression level of transforming growth factor  receptor II (TGFRII) and tropomyosin-1 (TPM1) through miR-21 These results show the pathway of exosome internalization and demonstrate that tumor cell-derived exosomes regulate target gene expression in normal cells. Using quantitative real-time PCR (RT-PCR) and immunoblot assay, it was demonstrated that PC12 cell-derived exosomes delivered miR-21 into bone marrow-derived mesenchymal stromal cells (BMSCs) and down-regulated the expression levels of their transforming growth factor  receptor II (TGFRII) and tropomyosin-1 (TPM1). These findings add insights into the endo-. Exosome Internalization and miRNA Delivery cytic pathway and the biological significance of tumor exosomes
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