Altered biodistribution of deglycosylated extracellular vesicles through enhanced cellular uptake
Extracellular vesicles (EVs) from cancer are delivered both proximal and distal organs. EVs are highly glycosylated at the surface where EVs interact with cells and therefore has an impact on their properties and biological functions. Aberrant glycosylation in cancer is associated with cancer progre...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022
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| Online Access: | https://hdl.handle.net/1721.1/141215 |
| _version_ | 1811097815507533824 |
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| author | Nishida-Aoki, N Tominaga, N Kosaka, N Ochiya, T |
| author_facet | Nishida-Aoki, N Tominaga, N Kosaka, N Ochiya, T |
| author_sort | Nishida-Aoki, N |
| collection | MIT |
| description | Extracellular vesicles (EVs) from cancer are delivered both proximal and distal organs. EVs are highly glycosylated at the surface where EVs interact with cells and therefore has an impact on their properties and biological functions. Aberrant glycosylation in cancer is associated with cancer progression and metastasis. However, the biological function of glycosylation on the surface of EV is uncovered. We first demonstrated differential glycosylation profiles of EVs and their originated cells, and distinct glycosylation profiles in a brain-metastatic subline BMD2a from its parental human breast cancer cell line, MDA-MB-231-luc-D3H2LN by lectin blot. We then investigated the roles of surface glycoconjugates on EV uptake. N- and/or O-glycosylation removal of fluorescent-labelled BMD2a EVs enhanced cellular uptake to endothelial cells, suggesting that surface glycosylation has inhibitory effects on cellular uptake. Biodistribution of glycosylation-deprived BMD2a EVs administrated intravenously into mice was further analysed ex vivo using near-infrared lipophilic dye. EVs treated with O-deglycosylation enzymes enhanced the accumulation of EVs to the lungs after 24 h from the injection, while N-deglycosylation did not markedly alter biodistribution. As the lungs are first organs in which intravenous blood flows, we suggest that surface glycosylation of cancer-derived EVs avoid promiscuous adhesion to proximal tissues to be delivered to distant organs. |
| first_indexed | 2024-09-23T17:05:24Z |
| format | Article |
| id | mit-1721.1/141215 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T17:05:24Z |
| publishDate | 2022 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1412152022-03-17T03:00:36Z Altered biodistribution of deglycosylated extracellular vesicles through enhanced cellular uptake Nishida-Aoki, N Tominaga, N Kosaka, N Ochiya, T Extracellular vesicles (EVs) from cancer are delivered both proximal and distal organs. EVs are highly glycosylated at the surface where EVs interact with cells and therefore has an impact on their properties and biological functions. Aberrant glycosylation in cancer is associated with cancer progression and metastasis. However, the biological function of glycosylation on the surface of EV is uncovered. We first demonstrated differential glycosylation profiles of EVs and their originated cells, and distinct glycosylation profiles in a brain-metastatic subline BMD2a from its parental human breast cancer cell line, MDA-MB-231-luc-D3H2LN by lectin blot. We then investigated the roles of surface glycoconjugates on EV uptake. N- and/or O-glycosylation removal of fluorescent-labelled BMD2a EVs enhanced cellular uptake to endothelial cells, suggesting that surface glycosylation has inhibitory effects on cellular uptake. Biodistribution of glycosylation-deprived BMD2a EVs administrated intravenously into mice was further analysed ex vivo using near-infrared lipophilic dye. EVs treated with O-deglycosylation enzymes enhanced the accumulation of EVs to the lungs after 24 h from the injection, while N-deglycosylation did not markedly alter biodistribution. As the lungs are first organs in which intravenous blood flows, we suggest that surface glycosylation of cancer-derived EVs avoid promiscuous adhesion to proximal tissues to be delivered to distant organs. 2022-03-16T15:34:54Z 2022-03-16T15:34:54Z 2020-01-01 2022-03-16T15:16:37Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/141215 Nishida-Aoki, N, Tominaga, N, Kosaka, N and Ochiya, T. 2020. "Altered biodistribution of deglycosylated extracellular vesicles through enhanced cellular uptake." Journal of Extracellular Vesicles, 9 (1). en 10.1080/20013078.2020.1713527 Journal of Extracellular Vesicles Creative Commons Attribution NonCommercial License 4.0 https://creativecommons.org/licenses/by-nc/4.0/ application/pdf Wiley Wiley |
| spellingShingle | Nishida-Aoki, N Tominaga, N Kosaka, N Ochiya, T Altered biodistribution of deglycosylated extracellular vesicles through enhanced cellular uptake |
| title | Altered biodistribution of deglycosylated extracellular vesicles through enhanced cellular uptake |
| title_full | Altered biodistribution of deglycosylated extracellular vesicles through enhanced cellular uptake |
| title_fullStr | Altered biodistribution of deglycosylated extracellular vesicles through enhanced cellular uptake |
| title_full_unstemmed | Altered biodistribution of deglycosylated extracellular vesicles through enhanced cellular uptake |
| title_short | Altered biodistribution of deglycosylated extracellular vesicles through enhanced cellular uptake |
| title_sort | altered biodistribution of deglycosylated extracellular vesicles through enhanced cellular uptake |
| url | https://hdl.handle.net/1721.1/141215 |
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