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Aged fibroblast-derived extracellular vesicles promote angiogenesis in melanoma

Advancing age is a negative prognostic factor for cutaneous melanoma. However, the role of extracellular vesicles (EVs) within the melanoma tumor microenvironment (TME) has remained unexplored in the context of aging. While the size and morphology of the EVs isolated from young vs. aged fibroblasts...

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Main Authors: Hüser, Laura (Author) , Chhabra, Yash (Author) , Gololobova, Olesia (Author) , Wang, Vania (Author) , Liu, Guanshu (Author) , Dixit, Agrani (Author) , Rocha, Murilo Ramos (Author) , Harper, Elizabeth I. (Author) , Fane, Mitchell E. (Author) , Marino-Bravante, Gloria E. (Author) , Zabransky, Daniel J. (Author) , Cai, Kathy Q. (Author) , Utikal, Jochen (Author) , Slusher, Barbara S. (Author) , Walston, Jeremy (Author) , Lipson, Evan J. (Author) , Witwer, Kenneth W. (Author) , Weeraratna, Ashani T. (Author)
Format: Article (Journal)
Language:English
Published: 24 September 2024
In: Cell reports
Year: 2024, Volume: 43, Issue: 9, Pages: 1-19
ISSN:2211-1247
DOI:10.1016/j.celrep.2024.114721
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.celrep.2024.114721
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2211124724010726
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Author Notes:Laura Hüser, Yash Chhabra, Olesia Gololobova, Vania Wang, Guanshu Liu, Agrani Dixit, Murilo Ramos Rocha, Elizabeth I. Harper, Mitchell E. Fane, Gloria E. Marino-Bravante, Daniel J. Zabransky, Kathy Q. Cai, Jochen Utikal, Barbara S. Slusher, Jeremy Walston, Evan J. Lipson, Kenneth W. Witwer, Ashani T. Weeraratna
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Summary:Advancing age is a negative prognostic factor for cutaneous melanoma. However, the role of extracellular vesicles (EVs) within the melanoma tumor microenvironment (TME) has remained unexplored in the context of aging. While the size and morphology of the EVs isolated from young vs. aged fibroblasts remained unaltered, the contents of the protein cargo were changed. Aging reduced the expression of the tetraspanin CD9 in both the dermal fibroblasts and released EVs. CD9 is a crucial regulator of EV cargo sorting. Modulating the CD9 expression in fibroblasts was sufficient to alter its levels in EVs. Mass spectrometry analysis of EVs released by CD9 knockdown (KD) vs. control cells revealed a significant increase in angiopoietin-like protein 2 (ANGPTL2), an angiogenesis promoter. Analysis of primary endothelial cells confirmed increased sprouting under CD9 KD conditions. Together, our data indicate that aged EVs play an important role in promoting a tumor-permissive microenvironment.
Item Description:Online verfügbar: 9. September 2024, Artikelversion: 9. September 2024
Gesehen am 12.11.2024
Physical Description:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2024.114721

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