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Cyclophilin A regulates secretion of tumour-derived extracellular vesicles
Extracellular Vesicles (EVs) are a heterogenous population of particles that play an important role in cell-cell communication in physiological and pathophysiological situations. In this study we reveal that the peptidyl prolyl isomerase Cyclophilin A (CypA) is enriched in cancer-derived EVs from a...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131927/ https://www.ncbi.nlm.nih.gov/pubmed/33984826 http://dx.doi.org/10.1016/j.tranon.2021.101112 |
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author | Wu, Yunjie Brennan, Kieran Fernández, Alfonso Blanco Mc Gee, Margaret M. |
author_facet | Wu, Yunjie Brennan, Kieran Fernández, Alfonso Blanco Mc Gee, Margaret M. |
author_sort | Wu, Yunjie |
collection | PubMed |
description | Extracellular Vesicles (EVs) are a heterogenous population of particles that play an important role in cell-cell communication in physiological and pathophysiological situations. In this study we reveal that the peptidyl prolyl isomerase Cyclophilin A (CypA) is enriched in cancer-derived EVs from a range of haematopoietic malignancies. CypA-enriched blood cancer EVs were taken up by normal monocytes independent of EV surface trypsin-sensitive proteins and potently stimulated pro-inflammatory MMP9 and IL-6 secretion. Further characterisation revealed that CypA is intravesicular, however, it is not present in all EVs derived from the haematopoietic cells, instead, it is predominantly located in high density EVs with a range of 1.15–1.18 g/ml. Furthermore, loss of CypA expression in haematological cancer cells attenuates high density EV-induced pro-inflammatory MMP9 and IL-6 secretion from monocytes. Mechanistically, we reveal that homozygous loss or siRNA knockdown of CypA expression significantly reduced the secretion of EVs in the range of 100–200 nm from blood cancer cells under normal and hypoxic conditions. Overall, this work reveals a novel role for CypA in cancer cell EV biogenesis. |
format | Online Article Text |
id | pubmed-8131927 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-81319272021-05-24 Cyclophilin A regulates secretion of tumour-derived extracellular vesicles Wu, Yunjie Brennan, Kieran Fernández, Alfonso Blanco Mc Gee, Margaret M. Transl Oncol Original Research Extracellular Vesicles (EVs) are a heterogenous population of particles that play an important role in cell-cell communication in physiological and pathophysiological situations. In this study we reveal that the peptidyl prolyl isomerase Cyclophilin A (CypA) is enriched in cancer-derived EVs from a range of haematopoietic malignancies. CypA-enriched blood cancer EVs were taken up by normal monocytes independent of EV surface trypsin-sensitive proteins and potently stimulated pro-inflammatory MMP9 and IL-6 secretion. Further characterisation revealed that CypA is intravesicular, however, it is not present in all EVs derived from the haematopoietic cells, instead, it is predominantly located in high density EVs with a range of 1.15–1.18 g/ml. Furthermore, loss of CypA expression in haematological cancer cells attenuates high density EV-induced pro-inflammatory MMP9 and IL-6 secretion from monocytes. Mechanistically, we reveal that homozygous loss or siRNA knockdown of CypA expression significantly reduced the secretion of EVs in the range of 100–200 nm from blood cancer cells under normal and hypoxic conditions. Overall, this work reveals a novel role for CypA in cancer cell EV biogenesis. Neoplasia Press 2021-05-10 /pmc/articles/PMC8131927/ /pubmed/33984826 http://dx.doi.org/10.1016/j.tranon.2021.101112 Text en © 2021 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Research Wu, Yunjie Brennan, Kieran Fernández, Alfonso Blanco Mc Gee, Margaret M. Cyclophilin A regulates secretion of tumour-derived extracellular vesicles |
title | Cyclophilin A regulates secretion of tumour-derived extracellular vesicles |
title_full | Cyclophilin A regulates secretion of tumour-derived extracellular vesicles |
title_fullStr | Cyclophilin A regulates secretion of tumour-derived extracellular vesicles |
title_full_unstemmed | Cyclophilin A regulates secretion of tumour-derived extracellular vesicles |
title_short | Cyclophilin A regulates secretion of tumour-derived extracellular vesicles |
title_sort | cyclophilin a regulates secretion of tumour-derived extracellular vesicles |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131927/ https://www.ncbi.nlm.nih.gov/pubmed/33984826 http://dx.doi.org/10.1016/j.tranon.2021.101112 |
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