Analysis of exosome release as a cellular response to MAPK pathway inhibition.
Exosome size distributions and numbers of exosomes released per cell are measured by asymmetric flow-field flow fractionation/multi-angle light scattering (A4F/MALS) for three thyroid cancer cell lines as a function of a treatment that inhibits MAPK signaling pathways in the cells. We show that these cell lines release exosomes with well-defined morphological features and size distributions that reflect a common biological process for their formation and release into the extracellular environment. We find that those cell lines with constitutive activation of the MAPK signaling pathway display MEK-dependent exosome release characterized by increased numbers of exosomes released per cell. Analysis of the measured exosome size distributions based on a generalized extreme value distribution model for exosome formation in intracellular multivesicular bodies highlights the importance of this experimental observable for delineating different mechanisms of vesicle formation and predicting how changes in exosome release can be modified by pathway inhibitors in a cell context-dependent manner.
William G. Lowrie Department of Chemical and Biomolecular Engineering, Department of Chemistry, Nanoscale Science and Engineering Center for Affordable Nanoenginering of Polymeric Biomedical Devices, Department of Internal Medicine, Division of Endocrinology Diabetes and Metabolism, Arthur G. James Comprehensive Cancer Center and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, United States.
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Agarwal
William G. Lowrie Department of Chemical and Biomolecular Engineering, Department of Chemistry, Nanoscale Science and Engineering Center for Affordable Nanoenginering of Polymeric Biomedical Devices, Department of Internal Medicine, Division of Endocrinology Diabetes and Metabolism, Arthur G. James Comprehensive Cancer Center and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, United States.
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Saji
William G. Lowrie Department of Chemical and Biomolecular Engineering, Department of Chemistry, Nanoscale Science and Engineering Center for Affordable Nanoenginering of Polymeric Biomedical Devices, Department of Internal Medicine, Division of Endocrinology Diabetes and Metabolism, Arthur G. James Comprehensive Cancer Center and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, United States.
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Lazaroff
William G. Lowrie Department of Chemical and Biomolecular Engineering, Department of Chemistry, Nanoscale Science and Engineering Center for Affordable Nanoenginering of Polymeric Biomedical Devices, Department of Internal Medicine, Division of Endocrinology Diabetes and Metabolism, Arthur G. James Comprehensive Cancer Center and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, United States.
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Palmer
William G. Lowrie Department of Chemical and Biomolecular Engineering, Department of Chemistry, Nanoscale Science and Engineering Center for Affordable Nanoenginering of Polymeric Biomedical Devices, Department of Internal Medicine, Division of Endocrinology Diabetes and Metabolism, Arthur G. James Comprehensive Cancer Center and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, United States.
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Ringel
William G. Lowrie Department of Chemical and Biomolecular Engineering, Department of Chemistry, Nanoscale Science and Engineering Center for Affordable Nanoenginering of Polymeric Biomedical Devices, Department of Internal Medicine, Division of Endocrinology Diabetes and Metabolism, Arthur G. James Comprehensive Cancer Center and Richard G. Solove Research Institute, The Ohio State University, Columbus, Ohio 43210, United States.
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Paulaitis
D055354:Exosomes / Q000378:metabolism*; D031521:Fractionation, Field Flow; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D012542:Scattering, Radiation; D014407:Tumor Cells, Cultured
D020930:MAP Kinase Kinase Kinases