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
{"title":"老化成纤维细胞衍生的细胞外囊泡促进黑色素瘤的血管生成","authors":"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","doi":"10.1016/j.celrep.2024.114721","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5000,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Aged fibroblast-derived extracellular vesicles promote angiogenesis in melanoma\",\"authors\":\"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\",\"doi\":\"10.1016/j.celrep.2024.114721\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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.</p>\",\"PeriodicalId\":9798,\"journal\":{\"name\":\"Cell reports\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.5000,\"publicationDate\":\"2024-09-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell reports\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.celrep.2024.114721\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell reports","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.celrep.2024.114721","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
年龄增长是皮肤黑色素瘤的一个不利预后因素。然而，细胞外囊泡（EVs）在黑色素瘤肿瘤微环境（TME）中的作用尚未被研究。虽然从年轻与衰老的成纤维细胞中分离出的EVs的大小和形态保持不变，但其中的蛋白质货物的含量却发生了变化。衰老降低了四跨蛋白 CD9 在真皮成纤维细胞和释放的 EVs 中的表达。CD9是EV货物分拣的关键调节因子。调节成纤维细胞中CD9的表达足以改变其在EVs中的水平。对CD9敲除（KD）与对照细胞释放的EV进行质谱分析发现，血管生成促进因子血管生成素样蛋白2（ANGPTL2）显著增加。对原代内皮细胞的分析证实，在 CD9 KD 条件下，血管萌发增加。总之，我们的数据表明，老化的 EV 在促进肿瘤容许的微环境中发挥着重要作用。
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 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.
期刊介绍：
Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted.
The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership.
The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
