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Metabolic reprogramming of stromal fibroblasts by melanoma exosome microRNA favours a pre-metastatic microenvironment

Local acidification of stroma is proposed to favour pre-metastatic niche formation but the mechanism of initiation is unclear. We investigated whether Human Melanoma-derived exosomes (HMEX) could reprogram human adult dermal fibroblasts (HADF) and cause extracellular acidification. HMEX were isolate...

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Autores principales: Shu, Shin La, Yang, Yunchen, Allen, Cheryl L., Maguire, Orla, Minderman, Hans, Sen, Arindam, Ciesielski, Michael J., Collins, Katherine A., Bush, Peter J., Singh, Prashant, Wang, Xue, Morgan, Martin, Qu, Jun, Bankert, Richard B., Whiteside, Theresa L., Wu, Yun, Ernstoff, Marc S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110845/
https://www.ncbi.nlm.nih.gov/pubmed/30150674
http://dx.doi.org/10.1038/s41598-018-31323-7
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author Shu, Shin La
Yang, Yunchen
Allen, Cheryl L.
Maguire, Orla
Minderman, Hans
Sen, Arindam
Ciesielski, Michael J.
Collins, Katherine A.
Bush, Peter J.
Singh, Prashant
Wang, Xue
Morgan, Martin
Qu, Jun
Bankert, Richard B.
Whiteside, Theresa L.
Wu, Yun
Ernstoff, Marc S.
author_facet Shu, Shin La
Yang, Yunchen
Allen, Cheryl L.
Maguire, Orla
Minderman, Hans
Sen, Arindam
Ciesielski, Michael J.
Collins, Katherine A.
Bush, Peter J.
Singh, Prashant
Wang, Xue
Morgan, Martin
Qu, Jun
Bankert, Richard B.
Whiteside, Theresa L.
Wu, Yun
Ernstoff, Marc S.
author_sort Shu, Shin La
collection PubMed
description Local acidification of stroma is proposed to favour pre-metastatic niche formation but the mechanism of initiation is unclear. We investigated whether Human Melanoma-derived exosomes (HMEX) could reprogram human adult dermal fibroblasts (HADF) and cause extracellular acidification. HMEX were isolated from supernatants of six melanoma cell lines (3 BRAF V600E mutant cell lines and 3 BRAF wild-type cell lines) using ultracentrifugation or Size Exclusion Chromatography (SEC). Rapid uptake of exosomes by HADF was demonstrated following 18 hours co-incubation. Exposure of HDAF to HMEX leads to an increase in aerobic glycolysis and decrease in oxidative phosphorylation (OXPHOS) in HADF, consequently increasing extracellular acidification. Using a novel immuno-biochip, exosomal miR-155 and miR-210 were detected in HMEX. These miRNAs were present in HMEX from all six melanoma cell lines and were instrumental in promoting glycolysis and inhibiting OXPHOS in tumour cells. Inhibition of miR-155 and miR-210 activity by transfection of miRNA inhibitors into HMEX reversed the exosome-induced metabolic reprogramming of HADF. The data indicate that melanoma-derived exosomes modulate stromal cell metabolism and may contribute to the creation of a pre-metastatic niche that promotes the development of metastasis.
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spelling pubmed-61108452018-08-30 Metabolic reprogramming of stromal fibroblasts by melanoma exosome microRNA favours a pre-metastatic microenvironment Shu, Shin La Yang, Yunchen Allen, Cheryl L. Maguire, Orla Minderman, Hans Sen, Arindam Ciesielski, Michael J. Collins, Katherine A. Bush, Peter J. Singh, Prashant Wang, Xue Morgan, Martin Qu, Jun Bankert, Richard B. Whiteside, Theresa L. Wu, Yun Ernstoff, Marc S. Sci Rep Article Local acidification of stroma is proposed to favour pre-metastatic niche formation but the mechanism of initiation is unclear. We investigated whether Human Melanoma-derived exosomes (HMEX) could reprogram human adult dermal fibroblasts (HADF) and cause extracellular acidification. HMEX were isolated from supernatants of six melanoma cell lines (3 BRAF V600E mutant cell lines and 3 BRAF wild-type cell lines) using ultracentrifugation or Size Exclusion Chromatography (SEC). Rapid uptake of exosomes by HADF was demonstrated following 18 hours co-incubation. Exposure of HDAF to HMEX leads to an increase in aerobic glycolysis and decrease in oxidative phosphorylation (OXPHOS) in HADF, consequently increasing extracellular acidification. Using a novel immuno-biochip, exosomal miR-155 and miR-210 were detected in HMEX. These miRNAs were present in HMEX from all six melanoma cell lines and were instrumental in promoting glycolysis and inhibiting OXPHOS in tumour cells. Inhibition of miR-155 and miR-210 activity by transfection of miRNA inhibitors into HMEX reversed the exosome-induced metabolic reprogramming of HADF. The data indicate that melanoma-derived exosomes modulate stromal cell metabolism and may contribute to the creation of a pre-metastatic niche that promotes the development of metastasis. Nature Publishing Group UK 2018-08-27 /pmc/articles/PMC6110845/ /pubmed/30150674 http://dx.doi.org/10.1038/s41598-018-31323-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Shu, Shin La
Yang, Yunchen
Allen, Cheryl L.
Maguire, Orla
Minderman, Hans
Sen, Arindam
Ciesielski, Michael J.
Collins, Katherine A.
Bush, Peter J.
Singh, Prashant
Wang, Xue
Morgan, Martin
Qu, Jun
Bankert, Richard B.
Whiteside, Theresa L.
Wu, Yun
Ernstoff, Marc S.
Metabolic reprogramming of stromal fibroblasts by melanoma exosome microRNA favours a pre-metastatic microenvironment
title Metabolic reprogramming of stromal fibroblasts by melanoma exosome microRNA favours a pre-metastatic microenvironment
title_full Metabolic reprogramming of stromal fibroblasts by melanoma exosome microRNA favours a pre-metastatic microenvironment
title_fullStr Metabolic reprogramming of stromal fibroblasts by melanoma exosome microRNA favours a pre-metastatic microenvironment
title_full_unstemmed Metabolic reprogramming of stromal fibroblasts by melanoma exosome microRNA favours a pre-metastatic microenvironment
title_short Metabolic reprogramming of stromal fibroblasts by melanoma exosome microRNA favours a pre-metastatic microenvironment
title_sort metabolic reprogramming of stromal fibroblasts by melanoma exosome microrna favours a pre-metastatic microenvironment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110845/
https://www.ncbi.nlm.nih.gov/pubmed/30150674
http://dx.doi.org/10.1038/s41598-018-31323-7
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