黑色素瘤分泌的黑色素小体可调节肿瘤相关巨噬细胞的多样化。

IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Journal Pub Date : 2024-09-01 Epub Date: 2024-05-08 DOI:10.1038/s44318-024-00103-7
Roma Parikh, Shivang Parikh, Daniella Berzin, Hananya Vaknine, Shai Ovadia, Daniela Likonen, Shoshana Greenberger, Alon Scope, Sharona Elgavish, Yuval Nevo, Inbar Plaschkes, Eran Nizri, Oren Kobiler, Avishai Maliah, Laureen Zaremba, Vishnu Mohan, Irit Sagi, Ruth Ashery-Padan, Yaron Carmi, Chen Luxenburg, Jörg D Hoheisel, Mehdi Khaled, Mitchell P Levesque, Carmit Levy
{"title":"黑色素瘤分泌的黑色素小体可调节肿瘤相关巨噬细胞的多样化。","authors":"Roma Parikh, Shivang Parikh, Daniella Berzin, Hananya Vaknine, Shai Ovadia, Daniela Likonen, Shoshana Greenberger, Alon Scope, Sharona Elgavish, Yuval Nevo, Inbar Plaschkes, Eran Nizri, Oren Kobiler, Avishai Maliah, Laureen Zaremba, Vishnu Mohan, Irit Sagi, Ruth Ashery-Padan, Yaron Carmi, Chen Luxenburg, Jörg D Hoheisel, Mehdi Khaled, Mitchell P Levesque, Carmit Levy","doi":"10.1038/s44318-024-00103-7","DOIUrl":null,"url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are important mediators of communication between cells. Here, we reveal a new mode of intercellular communication by melanosomes, large EVs secreted by melanocytes for melanin transport. Unlike small EVs, which are disintegrated within the receiver cell, melanosomes stay intact within them, gain a unique protein signature, and can then be further transferred to another cell as \"second-hand\" EVs. We show that melanoma-secreted melanosomes passaged through epidermal keratinocytes or dermal fibroblasts can be further engulfed by resident macrophages. This process leads to macrophage polarization into pro-tumor or pro-immune cell infiltration phenotypes. Melanosomes that are transferred through fibroblasts can carry AKT1, which induces VEGF secretion from macrophages in an mTOR-dependent manner, promoting angiogenesis and metastasis in vivo. In melanoma patients, macrophages that are co-localized with AKT1 are correlated with disease aggressiveness, and immunotherapy non-responders are enriched in macrophages containing melanosome markers. Our findings suggest that interactions mediated by second-hand extracellular vesicles contribute to the formation of the metastatic niche, and that blocking the melanosome cues of macrophage diversification could be helpful in halting melanoma progression.</p>","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"3553-3586"},"PeriodicalIF":9.4000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377571/pdf/","citationCount":"0","resultStr":"{\"title\":\"Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification.\",\"authors\":\"Roma Parikh, Shivang Parikh, Daniella Berzin, Hananya Vaknine, Shai Ovadia, Daniela Likonen, Shoshana Greenberger, Alon Scope, Sharona Elgavish, Yuval Nevo, Inbar Plaschkes, Eran Nizri, Oren Kobiler, Avishai Maliah, Laureen Zaremba, Vishnu Mohan, Irit Sagi, Ruth Ashery-Padan, Yaron Carmi, Chen Luxenburg, Jörg D Hoheisel, Mehdi Khaled, Mitchell P Levesque, Carmit Levy\",\"doi\":\"10.1038/s44318-024-00103-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Extracellular vesicles (EVs) are important mediators of communication between cells. Here, we reveal a new mode of intercellular communication by melanosomes, large EVs secreted by melanocytes for melanin transport. Unlike small EVs, which are disintegrated within the receiver cell, melanosomes stay intact within them, gain a unique protein signature, and can then be further transferred to another cell as \\\"second-hand\\\" EVs. We show that melanoma-secreted melanosomes passaged through epidermal keratinocytes or dermal fibroblasts can be further engulfed by resident macrophages. This process leads to macrophage polarization into pro-tumor or pro-immune cell infiltration phenotypes. Melanosomes that are transferred through fibroblasts can carry AKT1, which induces VEGF secretion from macrophages in an mTOR-dependent manner, promoting angiogenesis and metastasis in vivo. In melanoma patients, macrophages that are co-localized with AKT1 are correlated with disease aggressiveness, and immunotherapy non-responders are enriched in macrophages containing melanosome markers. Our findings suggest that interactions mediated by second-hand extracellular vesicles contribute to the formation of the metastatic niche, and that blocking the melanosome cues of macrophage diversification could be helpful in halting melanoma progression.</p>\",\"PeriodicalId\":50533,\"journal\":{\"name\":\"EMBO Journal\",\"volume\":\" \",\"pages\":\"3553-3586\"},\"PeriodicalIF\":9.4000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377571/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EMBO Journal\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1038/s44318-024-00103-7\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/8 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"EMBO Journal","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s44318-024-00103-7","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/8 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

细胞外囊泡(EVs)是细胞间通信的重要媒介。在这里,我们揭示了黑色素小体进行细胞间通信的一种新模式,黑色素小体是黑色素细胞为运输黑色素而分泌的大型EV。与在接收细胞内分解的小EV不同,黑色素体在接收细胞内保持完整,并获得独特的蛋白质特征,然后可以作为 "二手 "EV进一步转移到另一个细胞。我们的研究表明,通过表皮角质细胞或真皮成纤维细胞传递的黑色素瘤分泌的黑色素小体可被驻留的巨噬细胞进一步吞噬。这一过程会导致巨噬细胞极化为亲肿瘤或亲免疫细胞浸润表型。通过成纤维细胞转移的黑色素小体可携带 AKT1,AKT1 可通过 mTOR 依赖性方式诱导巨噬细胞分泌血管内皮生长因子,促进体内血管生成和转移。在黑色素瘤患者中,与AKT1共定位的巨噬细胞与疾病的侵袭性相关,免疫疗法无反应者的巨噬细胞中富含黑色素体标记。我们的研究结果表明,二手细胞外囊泡介导的相互作用促成了转移龛的形成,阻断巨噬细胞多样化的黑色素体线索有助于阻止黑色素瘤的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification.

Extracellular vesicles (EVs) are important mediators of communication between cells. Here, we reveal a new mode of intercellular communication by melanosomes, large EVs secreted by melanocytes for melanin transport. Unlike small EVs, which are disintegrated within the receiver cell, melanosomes stay intact within them, gain a unique protein signature, and can then be further transferred to another cell as "second-hand" EVs. We show that melanoma-secreted melanosomes passaged through epidermal keratinocytes or dermal fibroblasts can be further engulfed by resident macrophages. This process leads to macrophage polarization into pro-tumor or pro-immune cell infiltration phenotypes. Melanosomes that are transferred through fibroblasts can carry AKT1, which induces VEGF secretion from macrophages in an mTOR-dependent manner, promoting angiogenesis and metastasis in vivo. In melanoma patients, macrophages that are co-localized with AKT1 are correlated with disease aggressiveness, and immunotherapy non-responders are enriched in macrophages containing melanosome markers. Our findings suggest that interactions mediated by second-hand extracellular vesicles contribute to the formation of the metastatic niche, and that blocking the melanosome cues of macrophage diversification could be helpful in halting melanoma progression.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
EMBO Journal
EMBO Journal 生物-生化与分子生物学
CiteScore
18.90
自引率
0.90%
发文量
246
审稿时长
1.5 months
期刊介绍: The EMBO Journal has stood as EMBO's flagship publication since its inception in 1982. Renowned for its international reputation in quality and originality, the journal spans all facets of molecular biology. It serves as a platform for papers elucidating original research of broad general interest in molecular and cell biology, with a distinct focus on molecular mechanisms and physiological relevance. With a commitment to promoting articles reporting novel findings of broad biological significance, The EMBO Journal stands as a key contributor to advancing the field of molecular biology.
期刊最新文献
Author Correction: Single-cell transcriptomics stratifies organoid models of metabolic dysfunction-associated steatotic liver disease. Fibrillarin homologs regulate translation in divergent cell lineages during planarian homeostasis and regeneration. FNDC1 is a myokine that promotes myogenesis and muscle regeneration. Molecular condensation of the CO/NF-YB/NF-YC/FT complex gates floral transition in Arabidopsis. Sex-specific regulatory architecture of pancreatic islets from subjects with and without type 2 diabetes.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1