CD147 Mediates the Metabolic Reprogramming of Cancer Associated Fibroblasts Induced by EVs Released by Differentiating Cancer Stem Cells

Filomena Colella, Federica Calapà, Giulia Artemi, Erica Pazzaglia, Rita Colonna, Sara Vitale, Giacomo Lazzarino, Federica Vincenzoni, Micol Eleonora Fiori, Ruggero De Maria, Sara Lucchisani, Giannicola Genovese, Luigi Perelli, Barbara Tavazzi, Alessandro Sgambato, Donatella Lucchetti
{"title":"CD147 Mediates the Metabolic Reprogramming of Cancer Associated Fibroblasts Induced by EVs Released by Differentiating Cancer Stem Cells","authors":"Filomena Colella,&nbsp;Federica Calapà,&nbsp;Giulia Artemi,&nbsp;Erica Pazzaglia,&nbsp;Rita Colonna,&nbsp;Sara Vitale,&nbsp;Giacomo Lazzarino,&nbsp;Federica Vincenzoni,&nbsp;Micol Eleonora Fiori,&nbsp;Ruggero De Maria,&nbsp;Sara Lucchisani,&nbsp;Giannicola Genovese,&nbsp;Luigi Perelli,&nbsp;Barbara Tavazzi,&nbsp;Alessandro Sgambato,&nbsp;Donatella Lucchetti","doi":"10.1002/jex2.70039","DOIUrl":null,"url":null,"abstract":"<p>Several reports have demonstrated that CD147, an N-glycosylated protein that is exchanged by cells in soluble form or through small extracellular vesicles (sEVs), can promote cancer progression. However, its activity related to EVs in colorectal cancer (CRC) is still not fully understood. Previously, we showed that sEV secretion during CRC stem cell (CR-CSCs) differentiation is partially controlled by CD147, and that CD147-expressing sEVs (sEVs-CD147) activate a signalling cascade in recipient cells, inducing molecular invasive features in CR-CSCs. In the present study, we demonstrated that sEVs-CD147 increase the expression of myofibroblast and activation markers in cancer-associated fibroblasts (CAF). In sEVs-CD147-activated CAF, aerobic glycolysis was also triggered by the β-catenin signalling pathway and induced lactate release. These effects were associated with NFKβ upregulation and NO secretion that caused increased cytokines production and VEGF release, respectively. Furthermore, co-culture with CAF promoted CR-CSC invasivity in vitro and tumour growth in vivo. Spatial proteomics analysis confirmed in vivo the activation of fibroblasts and the modulation of their metabolic features, within their biological context, after their conditioning with CD147-expressing sEVs. Our findings indicate that sEV-packaged CD147 is involved in CAF activation, thus promoting tumour progression via stroma metabolism modification.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"4 3","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70039","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of extracellular biology","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jex2.70039","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Several reports have demonstrated that CD147, an N-glycosylated protein that is exchanged by cells in soluble form or through small extracellular vesicles (sEVs), can promote cancer progression. However, its activity related to EVs in colorectal cancer (CRC) is still not fully understood. Previously, we showed that sEV secretion during CRC stem cell (CR-CSCs) differentiation is partially controlled by CD147, and that CD147-expressing sEVs (sEVs-CD147) activate a signalling cascade in recipient cells, inducing molecular invasive features in CR-CSCs. In the present study, we demonstrated that sEVs-CD147 increase the expression of myofibroblast and activation markers in cancer-associated fibroblasts (CAF). In sEVs-CD147-activated CAF, aerobic glycolysis was also triggered by the β-catenin signalling pathway and induced lactate release. These effects were associated with NFKβ upregulation and NO secretion that caused increased cytokines production and VEGF release, respectively. Furthermore, co-culture with CAF promoted CR-CSC invasivity in vitro and tumour growth in vivo. Spatial proteomics analysis confirmed in vivo the activation of fibroblasts and the modulation of their metabolic features, within their biological context, after their conditioning with CD147-expressing sEVs. Our findings indicate that sEV-packaged CD147 is involved in CAF activation, thus promoting tumour progression via stroma metabolism modification.

Abstract Image

CD147介导分化癌症干细胞释放的ev诱导的癌症相关成纤维细胞代谢重编程
一些报道表明,CD147是一种n -糖基化蛋白,可通过细胞以可溶性形式或通过小细胞外囊泡(sev)进行交换,可促进癌症进展。然而,其在结直肠癌(CRC)中与EVs相关的活性尚不完全清楚。先前,我们发现CRC干细胞(CR-CSCs)分化过程中sEV的分泌部分受CD147控制,表达CD147的sEV (sEV -CD147)激活受体细胞中的信号级联,诱导CR-CSCs的分子侵袭特征。在本研究中,我们证明了sefs - cd147增加了肌成纤维细胞和癌症相关成纤维细胞(CAF)中激活标记物的表达。在sews - cd147激活的CAF中,β-catenin信号通路也触发有氧糖酵解并诱导乳酸释放。这些作用与NFKβ上调和NO分泌有关,分别导致细胞因子产生和VEGF释放增加。此外,与CAF共培养可促进体外CR-CSC侵袭性和体内肿瘤生长。空间蛋白质组学分析在体内证实了成纤维细胞的激活及其代谢特征的调节,在其生物学背景下,在它们被表达cd147的sev调节后。我们的研究结果表明,sev包装的CD147参与CAF激活,从而通过基质代谢改变促进肿瘤进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信