Aged Fibroblast-derived Extracellular Vesicles Promote Angiogenesis in Melanoma

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2024 Sep 10

PMID 39255061

Authors

Laura Huser

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

Affiliations

Soon will be listed here.

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.

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