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.
Keywords:
Cell-Cell Interaction; Endocytosis; Exosome; Extracellular Vesicles; microRNA (miRNA).
© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biological Transport, Active
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Caveolae / metabolism
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Caveolin 1 / antagonists & inhibitors
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Caveolin 1 / genetics
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Caveolin 1 / metabolism
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Cell Line
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Clathrin Heavy Chains / antagonists & inhibitors
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Clathrin Heavy Chains / genetics
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Clathrin Heavy Chains / metabolism*
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Dynamin II / antagonists & inhibitors
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Dynamin II / genetics
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Dynamin II / metabolism
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Endocytosis
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Exosomes / metabolism*
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Gene Expression Regulation
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Gene Knockdown Techniques
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Mesenchymal Stem Cells / metabolism
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MicroRNAs / genetics*
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MicroRNAs / metabolism*
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PC12 Cells
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Phagocytosis
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Pinocytosis
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Rats
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Receptor, Transforming Growth Factor-beta Type II
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Receptors, Transforming Growth Factor beta / genetics
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Receptors, Transforming Growth Factor beta / metabolism
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Tropomyosin / genetics
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Tropomyosin / metabolism
Substances
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Cav1 protein, rat
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Caveolin 1
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MicroRNAs
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Receptors, Transforming Growth Factor beta
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Tpm1 protein, rat
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Tropomyosin
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mirn21 microRNA, rat
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Clathrin Heavy Chains
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Protein Serine-Threonine Kinases
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Receptor, Transforming Growth Factor-beta Type II
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Dynamin II