Global and single-cell proteomics view of the co-evolution between neural progenitors and breast cancer cells in a co-culture model.

IF 9.7 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL EBioMedicine Pub Date : 2024-10-01 Epub Date: 2024-09-04 DOI:10.1016/j.ebiom.2024.105325
Ole Vidhammer Bjørnstad, Manuel Carrasco, Kenneth Finne, Vandana Ardawatia, Ingeborg Winge, Cecilie Askeland, Jarle B Arnes, Gøril Knutsvik, Dimitrios Kleftogiannis, Joao A Paulo, Lars A Akslen, Heidrun Vethe
{"title":"Global and single-cell proteomics view of the co-evolution between neural progenitors and breast cancer cells in a co-culture model.","authors":"Ole Vidhammer Bjørnstad, Manuel Carrasco, Kenneth Finne, Vandana Ardawatia, Ingeborg Winge, Cecilie Askeland, Jarle B Arnes, Gøril Knutsvik, Dimitrios Kleftogiannis, Joao A Paulo, Lars A Akslen, Heidrun Vethe","doi":"10.1016/j.ebiom.2024.105325","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Presence of nerves in tumours, by axonogenesis and neurogenesis, is gaining increased attention for its impact on cancer initiation and development, and the new field of cancer neuroscience is emerging. A recent study in prostate cancer suggested that the tumour microenvironment may influence cancer progression by recruitment of Doublecortin (DCX)-expressing neural progenitor cells (NPCs). However, the presence of such cells in human breast tumours has not been comprehensively explored.</p><p><strong>Methods: </strong>Here, we investigate the presence of DCX-expressing cells in breast cancer stromal tissue from patients using Imaging Mass Cytometry. Single-cell analysis of 372,468 cells across histopathological images of 107 breast cancers enabled spatial resolution of neural elements in the stromal compartment in correlation with clinicopathological features of these tumours. In parallel, we established a 3D in vitro model mimicking breast cancer neural progenitor-innervation and examined the two cell types as they co-evolved in co-culture by using mass spectrometry-based global proteomics.</p><p><strong>Findings: </strong>Stromal presence of DCX + cells is associated with tumours of higher histological grade, a basal-like phenotype, and shorter patient survival in tumour tissue from patients with breast cancer. Global proteomics analysis revealed significant changes in the proteomic landscape of both breast cancer cells and neural progenitors in co-culture.</p><p><strong>Interpretation: </strong>These results support that neural involvement plays an active role in breast cancer and warrants further studies on the relevance of nerve elements for tumour progression.</p><p><strong>Funding: </strong>This work was supported by the Research Council of Norway through its Centre of Excellence funding scheme, project number 223250 (to L.A.A), the Norwegian Cancer Society (to L.A.A. and H.V.), the Regional Health Trust Western Norway (Helse Vest) (to L.A.A.), the Meltzer Research Fund (to H.V.) and the National Institutes of Health (NIH)/NIGMS grant R01 GM132129 (to J.A.P.).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":null,"pages":null},"PeriodicalIF":9.7000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404160/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"EBioMedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ebiom.2024.105325","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/4 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Presence of nerves in tumours, by axonogenesis and neurogenesis, is gaining increased attention for its impact on cancer initiation and development, and the new field of cancer neuroscience is emerging. A recent study in prostate cancer suggested that the tumour microenvironment may influence cancer progression by recruitment of Doublecortin (DCX)-expressing neural progenitor cells (NPCs). However, the presence of such cells in human breast tumours has not been comprehensively explored.

Methods: Here, we investigate the presence of DCX-expressing cells in breast cancer stromal tissue from patients using Imaging Mass Cytometry. Single-cell analysis of 372,468 cells across histopathological images of 107 breast cancers enabled spatial resolution of neural elements in the stromal compartment in correlation with clinicopathological features of these tumours. In parallel, we established a 3D in vitro model mimicking breast cancer neural progenitor-innervation and examined the two cell types as they co-evolved in co-culture by using mass spectrometry-based global proteomics.

Findings: Stromal presence of DCX + cells is associated with tumours of higher histological grade, a basal-like phenotype, and shorter patient survival in tumour tissue from patients with breast cancer. Global proteomics analysis revealed significant changes in the proteomic landscape of both breast cancer cells and neural progenitors in co-culture.

Interpretation: These results support that neural involvement plays an active role in breast cancer and warrants further studies on the relevance of nerve elements for tumour progression.

Funding: This work was supported by the Research Council of Norway through its Centre of Excellence funding scheme, project number 223250 (to L.A.A), the Norwegian Cancer Society (to L.A.A. and H.V.), the Regional Health Trust Western Norway (Helse Vest) (to L.A.A.), the Meltzer Research Fund (to H.V.) and the National Institutes of Health (NIH)/NIGMS grant R01 GM132129 (to J.A.P.).

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
从全局和单细胞蛋白质组学视角观察神经祖细胞和乳腺癌细胞在共培养模型中的共同演化。
背景:肿瘤中神经的轴突生成和神经发生对癌症的发生和发展的影响日益受到关注,癌症神经科学这一新领域正在兴起。最近一项关于前列腺癌的研究表明,肿瘤微环境可能会通过招募表达双皮质素(DCX)的神经祖细胞(NPCs)来影响癌症的进展。方法:在此,我们使用成像质谱细胞计数法研究了患者乳腺癌基质组织中是否存在表达 DCX 的细胞。我们对 107 例乳腺癌组织病理图像中的 372,468 个细胞进行了单细胞分析,从而获得了基质区神经元的空间分辨率以及这些肿瘤的临床病理特征。与此同时,我们建立了一个模拟乳腺癌神经祖细胞神经支配的三维体外模型,并利用基于质谱的全蛋白质组学研究了两种细胞类型在共培养过程中的共同进化:研究结果:在乳腺癌患者的肿瘤组织中,DCX +细胞基质的存在与组织学级别较高的肿瘤、基底样表型和较短的患者生存期有关。全局蛋白质组学分析表明,乳腺癌细胞和神经祖细胞在共培养过程中的蛋白质组结构发生了显著变化:这些结果支持神经参与在乳腺癌中发挥了积极作用,因此有必要进一步研究神经元素与肿瘤进展的相关性:这项工作得到了挪威研究理事会(Research Council of Norway)卓越中心资助计划(项目编号:223250,资助人:L.A.A.)、挪威癌症协会(资助人:L.A.A.和H.V.)、挪威西部地区健康信托基金(Helse Vest)(资助人:L.A.A.)、梅尔泽研究基金(资助人:H.V.)和美国国立卫生研究院(NIH)/美国国立卫生研究院(NIGMS)R01 GM132129基金(资助人:J.A.P.)的支持。
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 去求助
来源期刊
EBioMedicine
EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍: eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.
期刊最新文献
Adoptive T cell therapies for solid tumors: T(I)ME is of the essence. Protecting vulnerable populations in extreme heat - a growing and pervasive health challenge. Identifying WHO global priority endemic pathogens for vaccine research and development (R&D) using multi-criteria decision analysis (MCDA): an objective of the Immunization Agenda 2030. Association between seizure reduction during ketogenic diet treatment of epilepsy and changes in circulatory metabolites and gut microbiota composition. Identification of late-stage tau accumulation using plasma phospho-tau217.
×
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