ArticleCell reports2024
Aged fibroblast-derived extracellular vesicles promote angiogenesis in melanoma.
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Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13citing papers in PubMed
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Who cites it
13 citing papers in PubMed.
- Unraveling the Plasma Extracellular Vesicles Proteome: Predictors of Resistance in Immunotherapy of Advanced Melanoma.International journal of cancer · 2026Article
- Extracellular vesicles and epigenetic aging clocks in tissue aging: an exosome-focused conceptual framework with a focus on skin.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Review
- Protocol for generation, time-course imaging, and automated quality control of 3D spheroid invasion using TRACEQC.STAR protocols · 2026Article
- Novel insights into extracellular vesicles: An update on biomolecules, immunomodulation and clinical strategies in skin melanoma.Clinical and translational medicine · 2026Review
- Combining Spatial Transcriptomics and Machine Learning Unravels Fibroblast-Related Biomarkers in Ulcerative Colitis.Inflammation · 2026Article
- Crosstalk between Extracellular Vesicles and the Tumor Microenvironment: Mechanistic Insights and Therapeutic Opportunities.Oncology research · 2026Review
- Review
- Cutaneous Melanoma in the Context of Aging.Medicina (Kaunas, Lithuania) · 2025Review
- Stromal senescence contributes to age-related increases in cancer.Nature reviews. Cancer · 2025Review
- Extracellular Vesicles Derived from Breast Cancer Cells: Emerging Biomarkers of Tumor Progression and Metastasis.Biomolecules · 2025Review
- A Paradigm Shift in SSTI Management: The Multifunctional Role of Extracellular Vesicles.International journal of molecular sciences · 2025Review
- Extracellular vesicles in age-related diseases: disease pathogenesis, intervention, and biomarker.Stem cell research & therapy · 2025Review
- Oncolytic virus therapy in the elderly: immune frailty, challenges, and perspectives.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
18 authors.
Laura HüserDepartment of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA; Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany; DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.
Yash ChhabraDepartment of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA; Research Program Cancer Signaling and Microenvironment, Fox Chase Institute for Cancer Research, Philadelphia, PA, USA.
Olesia GololobovaDepartment of Molecular and Comparative Pathobiology, Johns Hopkins Medicine, Baltimore, MD, USA.
Vania WangDepartment of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Guanshu LiuDepartment of Radiology and Radiological Science, Johns Hopkins Medicine, Baltimore, MD, USA.
Agrani DixitDepartment of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Murilo Ramos RochaDepartment of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Elizabeth I HarperDepartment of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Mitchell E FaneDepartment of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA; Research Program Cancer Signaling and Microenvironment, Fox Chase Institute for Cancer Research, Philadelphia, PA, USA.
Gloria E Marino-BravanteDepartment of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Daniel J ZabranskyDepartment of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Kathy Q CaiResearch Program Cancer Signaling and Microenvironment, Fox Chase Institute for Cancer Research, Philadelphia, PA, USA.
Jochen UtikalSkin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany; DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.
Barbara S SlusherJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jeremy WalstonDepartment of Medicine - Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology - Hematologic Malignancies, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Evan J LipsonDepartment of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA; Bloomberg Kimmel Institute for Cancer Immunotherapy, Baltimore, MD, USA.
Kenneth W WitwerDepartment of Molecular and Comparative Pathobiology, Johns Hopkins Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ashani T WeeraratnaDepartment of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: aweeraratna@jhu.edu.
Funding
Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6MTargeting the MAP and PI3 Kinase Pathways in MelanomaP01CA114046 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F, WEERARATNA, ASHANI T · 2008 to 2023
$37.1MTherapeutic CoreP30MH075673 · NIMH · JOHNS HOPKINS UNIVERSITY · PI Leah Helane Rubin · 2006 to 2026
$33.2MONCOLOGY: CHEMOTHERAPY, IMMUNOLOGY, BIOLOGYT32CA009071 · NCI · JOHNS HOPKINS UNIVERSITY · PI Mary Y Armanios, Nilofer S. Azad · 1985 to 2026
$12.8MT32: Predoctoral and Postdoctoral Training Program in Nanotechnology for Cancer ResearchT32CA153952 · NCI · JOHNS HOPKINS UNIVERSITY · PI Denis Wirtz · 2015 to 2026
$3.5MA plasticity and reprogramming paradigm for therapy resistance at the single cell levelU01CA227550 · NCI · UNIVERSITY OF PENNSYLVANIA · PI RADHAKRISHNAN, RAVI, RAJ, ARJUN · 2018 to 2022
$3.3MAn integrated approach to melanoma metastasis and therapy resistance: effects of age-related changes in the ECM and the biomechanics of the skinR01CA232256 · NCI · WISTAR INSTITUTE · PI CUKIERMAN, EDNA, RAJ, ARJUN · 2019 to 2023
$3.0MDevelopment of neutral sphingomyelinase 2 (nSMase2) inhibitors for the treatment of Alzheimer's diseaseR01AG084728 · NIA · JOHNS HOPKINS UNIVERSITY · PI Rana Rais, Barbara Stauch Slusher · 2023 to 2026
$2.8MDendrimer-conjugated nSMase2 inhibitor as a novel therapeutic approach for Alzheimer's DiseaseR01AG063831 · NIA · JOHNS HOPKINS UNIVERSITY · PI RAIS, RANA, RANGARAMANUJAM, KANNAN · 2020 to 2024
$2.3MEffect of the aged microenvironment on tumor dormancyR01CA207935 · NCI · WISTAR INSTITUTE · PI WEERARATNA, ASHANI T · 2017 to 2021
$2.0MThe role of MER/PROS1 in promoting stromal induced emergence from metastatic melanoma dormancyR00CA263017 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI FANE, MITCHELL EDWARD · 2023 to 2025
$747kIntegrative Analysis of the Aging Peritoneum in Metastatic ReceptivityK00AG068527 · NIA · JOHNS HOPKINS UNIVERSITY · PI HARPER, ELIZABETH · 2023 to 2025
$223kNCI NIH HHS F31 CA261065NCI NIH HHS K99 CA263017NCI NIH HHS P01 CA114046NCI NIH HHS P30 CA006973NCI NIH HHS R00 CA263017NCI NIH HHS R01 CA207935NCI NIH HHS R01 CA232256NCI NIH HHS T32 CA009071NCI NIH HHS T32 CA153952NCI NIH HHS U01 CA227550NIA NIH HHS K00 AG068527NIA NIH HHS R01 AG063831NIA NIH HHS R01 AG084728NIMH NIH HHS P30 MH075673
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.
Indexed as
Extracellular VesiclesFibroblastsMelanomaNeovascularization, PathologicTetraspanin 29AgingAngiogenesisAnimalsCell Line, TumorEndothelial CellsHumansSkin NeoplasmsTumor MicroenvironmentCD9 protein, humanTetraspanin 29agingangioepoetin ligand 2 (ANGPTL2)angiogenesisCD9CP: Cancerexosomesextracellular vesiclesfibroblastsmelanoma
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.