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Aged fibroblast-derived extracellular vesicles promote angiogenesis in melanoma.
- Source :
-
Cell reports [Cell Rep] 2024 Sep 24; Vol. 43 (9), pp. 114721. Date of Electronic Publication: 2024 Sep 09. - Publication Year :
- 2024
-
Abstract
- 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.<br />Competing Interests: Declaration of interests A.T.W. is on the boards of reGAIN Therapeutics and the Melanoma Research Foundation and the scientific advisory committee of the V Foundation. D.J.Z. reports grant funding (paid to Johns Hopkins University) from Roche/Genentech.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Tumor Microenvironment
Cell Line, Tumor
Skin Neoplasms pathology
Skin Neoplasms metabolism
Skin Neoplasms genetics
Aging metabolism
Aging pathology
Endothelial Cells metabolism
Endothelial Cells pathology
Animals
Angiogenesis
Extracellular Vesicles metabolism
Melanoma metabolism
Melanoma pathology
Neovascularization, Pathologic metabolism
Neovascularization, Pathologic pathology
Fibroblasts metabolism
Fibroblasts pathology
Tetraspanin 29 metabolism
Tetraspanin 29 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 43
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 39255061
- Full Text :
- https://doi.org/10.1016/j.celrep.2024.114721