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Vacuole-inducing compounds that disrupt endolysosomal trafficking stimulate production of exosomes by glioblastoma cells

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Abstract

Exosomes are produced from mammalian cells when multivesicular endosomes fuse with the plasma membrane, releasing their intralumenal vesicles. In this study we assessed the effects of MOPIPP, a novel indole-based chalcone, and vacuolin-1, a distinct triazine-based compound, on exosome production in cultured glioblastoma and 293T cells. Both compounds promote vacuolization of late endosome compartments and interfere with trafficking of late endosomes to lysosomes, without significant cytotoxicity. The results show that vacuolated cells treated with these compounds release exosomes with morphologies similar to untreated controls. However, both compounds trigger multi-fold increases in release of exosome marker proteins (e.g., CD63, Alix) in exosome fractions collected from equivalent numbers of cells. Despite the marked increase in exosome production, the profiles of selected miRNA cargoes carried by the exosomes were generally similar in cells treated with the compounds. Insofar as MOPIPP and vacuolin-1 seem able to increase the overall yield of exosomes from cultured cells, they might be useful for efforts to develop exosome-based therapeutics.

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Acknowledgements

We thank Christopher J. Trabbic and Paul W. Erhardt for supplying MOPIPP, and William T. Gunning III for assistance with electron microscopy of cells. This work was supported by NIH Grant R01 CA115495 and by the Harold and Helen McMaster Endowment for Biochemistry and Molecular Biology.

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  1. Department of Biochemistry and Cancer Biology, University of Toledo College of Medicine and Life Sciences, 3000 Arlington Avenue, Toledo, OH, 43617, USA

    Zehui Li, Nneka E. Mbah & William A. Maltese

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  1. Zehui Li
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  2. Nneka E. Mbah
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  3. William A. Maltese
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Correspondence to William A. Maltese.

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Li, Z., Mbah, N.E. & Maltese, W.A. Vacuole-inducing compounds that disrupt endolysosomal trafficking stimulate production of exosomes by glioblastoma cells. Mol Cell Biochem 439, 1–9 (2018). https://doi.org/10.1007/s11010-017-3130-x

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  • DOI: https://doi.org/10.1007/s11010-017-3130-x

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