Exosome Uptake through Clathrin-mediated Endocytosis and Macropinocytosis and Mediating miR-21 Delivery*

By Tian Tian, Yanliang Zhu, Yueyuan Zhou, G. Liang, Yuanyuan Wang, Feihu Hu, Zhong-Dang Xiao. Journal of Biological Chemistry, 2014

646 citations recorded by the source corpus.

Background: 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 TGFβRII and TPM1 through miR-21. Conclusion: The results dissect the pathway of exosome internalization and demonstrate their regulation ability. Significance: These findings enhanced our knowledge of the internalization and function of tumor exosomes. 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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/caf2229ad425ba7b9fafdab447eccdfe3af9b04e

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In Molecular Biology

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