A novel strategy of transferring NIS protein to cells using extracellular vesicles leads to increase in iodine uptake and cytotoxicity

Seung Hyun Son,1,2,* Prakash Gangadaran,1,2,* Byeong-Cheol Ahn1,2 1Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea *These authors contribut...

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Autores principales:	Son SH, Gangadaran P, Ahn B
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	sodium iodide symporter (NIS) extracellular vesicle iodine uptake hepato-cellular carcinoma Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/379b061d504c431c9eb6cacdb3b989d7
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spelling	oai:doaj.org-article:379b061d504c431c9eb6cacdb3b989d72021-12-02T05:47:12ZA novel strategy of transferring NIS protein to cells using extracellular vesicles leads to increase in iodine uptake and cytotoxicity1178-2013https://doaj.org/article/379b061d504c431c9eb6cacdb3b989d72019-03-01T00:00:00Zhttps://www.dovepress.com/a-novel-strategy-of-transferring-nis-protein-to-cells-using-extracellu-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Seung Hyun Son,1,2,* Prakash Gangadaran,1,2,* Byeong-Cheol Ahn1,2 1Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea *These authors contributed equally to this work Background: This study was designed to explore a novel approach for transferring NIS protein to cells using extracellular vesicle (EV) and enhancing iodine avidity in hepatocellular carcinoma (HCC) cells.Methods: We transfected the HCC cells (Huh7) with NIS gene, designated as Huh7/NIS, and isolated the EVs from them. Presence of NIS protein in EVs and EV-mediated transport of NIS protein to recipient Huh7 cells were tested using Western blotting. We also examined radioiodine uptake in Huh7 cells treated with EV-Huh7/NIS.Results: Successful transfer of NIS protein into Huh7 cells was confirmed by WB and microscopy. EVs showed high levels of NIS protein in them. Treatment of Huh7 cells with EV-Huh7/NIS increased the NIS protein level and enhanced 125I uptake in recipient Huh7 cells. In addition, EV-huh7/NIS pre-treatment enhanced the cytotoxicity of 131I therapy against Huh7 cells by inducing increased DNA damage/increased γH2A.X foci formation. Conclusion: This is the first-of-its-kind demonstration of successful transportation of the NIS protein to cells via EVs, which increased radioiodine uptake. This approach can revert radioiodine-resistant cancers into radioiodine-sensitive cancers. Keywords: sodium iodide symporter (NIS), extracellular vesicle, iodine uptake, hepato-cellular carcinoma  Son SHGangadaran PAhn BDove Medical Pressarticlesodium iodide symporter (NIS)extracellular vesicleiodine uptakehepato-cellular carcinomaMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 1779-1787 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	sodium iodide symporter (NIS) extracellular vesicle iodine uptake hepato-cellular carcinoma Medicine (General) R5-920
spellingShingle	sodium iodide symporter (NIS) extracellular vesicle iodine uptake hepato-cellular carcinoma Medicine (General) R5-920 Son SH Gangadaran P Ahn B A novel strategy of transferring NIS protein to cells using extracellular vesicles leads to increase in iodine uptake and cytotoxicity
description	Seung Hyun Son,1,2,* Prakash Gangadaran,1,2,* Byeong-Cheol Ahn1,2 1Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea *These authors contributed equally to this work Background: This study was designed to explore a novel approach for transferring NIS protein to cells using extracellular vesicle (EV) and enhancing iodine avidity in hepatocellular carcinoma (HCC) cells.Methods: We transfected the HCC cells (Huh7) with NIS gene, designated as Huh7/NIS, and isolated the EVs from them. Presence of NIS protein in EVs and EV-mediated transport of NIS protein to recipient Huh7 cells were tested using Western blotting. We also examined radioiodine uptake in Huh7 cells treated with EV-Huh7/NIS.Results: Successful transfer of NIS protein into Huh7 cells was confirmed by WB and microscopy. EVs showed high levels of NIS protein in them. Treatment of Huh7 cells with EV-Huh7/NIS increased the NIS protein level and enhanced 125I uptake in recipient Huh7 cells. In addition, EV-huh7/NIS pre-treatment enhanced the cytotoxicity of 131I therapy against Huh7 cells by inducing increased DNA damage/increased γH2A.X foci formation. Conclusion: This is the first-of-its-kind demonstration of successful transportation of the NIS protein to cells via EVs, which increased radioiodine uptake. This approach can revert radioiodine-resistant cancers into radioiodine-sensitive cancers. Keywords: sodium iodide symporter (NIS), extracellular vesicle, iodine uptake, hepato-cellular carcinoma
format	article
author	Son SH Gangadaran P Ahn B
author_facet	Son SH Gangadaran P Ahn B
author_sort	Son SH
title	A novel strategy of transferring NIS protein to cells using extracellular vesicles leads to increase in iodine uptake and cytotoxicity
title_short	A novel strategy of transferring NIS protein to cells using extracellular vesicles leads to increase in iodine uptake and cytotoxicity
title_full	A novel strategy of transferring NIS protein to cells using extracellular vesicles leads to increase in iodine uptake and cytotoxicity
title_fullStr	A novel strategy of transferring NIS protein to cells using extracellular vesicles leads to increase in iodine uptake and cytotoxicity
title_full_unstemmed	A novel strategy of transferring NIS protein to cells using extracellular vesicles leads to increase in iodine uptake and cytotoxicity
title_sort	novel strategy of transferring nis protein to cells using extracellular vesicles leads to increase in iodine uptake and cytotoxicity
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/379b061d504c431c9eb6cacdb3b989d7
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A novel strategy of transferring NIS protein to cells using extracellular vesicles leads to increase in iodine uptake and cytotoxicity

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