Lung tumor organoids migrate as cell clusters containing cancer stem cells under hypoxic condition

IF 2.4 4区 生物学 Q4 CELL BIOLOGY
Yanjiao Li, Jiarong Zou, Yanhua Fang, Jianing Zuo, Ruoyu Wang, Shanshan Liang
{"title":"Lung tumor organoids migrate as cell clusters containing cancer stem cells under hypoxic condition","authors":"Yanjiao Li,&nbsp;Jiarong Zou,&nbsp;Yanhua Fang,&nbsp;Jianing Zuo,&nbsp;Ruoyu Wang,&nbsp;Shanshan Liang","doi":"10.1111/boc.202400081","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Tumor hypoxia reshapes the microenvironment, driving progression, invasion, metastasis, and therapy resistance. Patient-derived tumor organoids, formed under three-dimensional conditions, preserve cellular heterogeneity and nutrient gradients, making them ideal for studying hypoxia-induced tumor responses. This study examines hypoxia-induced changes in lung tumor organoids from two patients, focusing on tumor-associated markers, stem cell markers, and migration capabilities.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Our findings demonstrate that hypoxia distinctively modulates the expression of lung cancer markers thyroid transcription factor-1, cytokeratin 7, and ΔNP63 variant. Hypoxia also induces the upregulation of stem cell-associated markers, resulting in an increased proportion of cancer stem cells. Furthermore, hypoxic lung tumor organoids exhibit unique migratory behavior upon reoxygenation, driven by epithelial-mesenchymal transition and the elevated expression of matrix metalloproteinases 7 and matrix metalloproteinases 9, indicating their enhanced invasive potential.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>These findings highlight the value of lung tumor organoids as models for studying hypoxia's complex role in lung cancer. Hypoxia significantly modulates lung tumor organoids growth, stemness, and migratory behavior, providing critical insights into tumor progression and therapy resistance.</p>\n </section>\n </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 2","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biology of the Cell","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/boc.202400081","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background

Tumor hypoxia reshapes the microenvironment, driving progression, invasion, metastasis, and therapy resistance. Patient-derived tumor organoids, formed under three-dimensional conditions, preserve cellular heterogeneity and nutrient gradients, making them ideal for studying hypoxia-induced tumor responses. This study examines hypoxia-induced changes in lung tumor organoids from two patients, focusing on tumor-associated markers, stem cell markers, and migration capabilities.

Results

Our findings demonstrate that hypoxia distinctively modulates the expression of lung cancer markers thyroid transcription factor-1, cytokeratin 7, and ΔNP63 variant. Hypoxia also induces the upregulation of stem cell-associated markers, resulting in an increased proportion of cancer stem cells. Furthermore, hypoxic lung tumor organoids exhibit unique migratory behavior upon reoxygenation, driven by epithelial-mesenchymal transition and the elevated expression of matrix metalloproteinases 7 and matrix metalloproteinases 9, indicating their enhanced invasive potential.

Conclusions

These findings highlight the value of lung tumor organoids as models for studying hypoxia's complex role in lung cancer. Hypoxia significantly modulates lung tumor organoids growth, stemness, and migratory behavior, providing critical insights into tumor progression and therapy resistance.

Abstract Image

肺肿瘤类器官在缺氧条件下作为含有肿瘤干细胞的细胞团迁移
肿瘤缺氧重塑微环境,驱动肿瘤进展、侵袭、转移和治疗抵抗。患者来源的肿瘤类器官在三维条件下形成,保持细胞异质性和营养梯度,使其成为研究缺氧诱导肿瘤反应的理想选择。本研究检测了缺氧诱导的两例患者肺肿瘤类器官的变化,重点关注肿瘤相关标志物、干细胞标志物和迁移能力。结果缺氧可显著调节肺癌标志物甲状腺转录因子-1、细胞角蛋白7和ΔNP63变体的表达。缺氧还会诱导干细胞相关标记物的上调,导致癌症干细胞的比例增加。此外,低氧肺肿瘤类器官在再氧化时表现出独特的迁移行为,由上皮-间质转化和基质金属蛋白酶7和基质金属蛋白酶9的表达升高驱动,表明其侵袭潜力增强。结论这些发现突出了肺肿瘤类器官作为研究缺氧在肺癌中的复杂作用模型的价值。缺氧显著调节肺肿瘤类器官的生长、干性和迁移行为,为肿瘤进展和治疗抵抗提供了重要的见解。
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
Biology of the Cell
Biology of the Cell 生物-细胞生物学
CiteScore
5.30
自引率
0.00%
发文量
53
审稿时长
>12 weeks
期刊介绍: The journal publishes original research articles and reviews on all aspects of cellular, molecular and structural biology, developmental biology, cell physiology and evolution. It will publish articles or reviews contributing to the understanding of the elementary biochemical and biophysical principles of live matter organization from the molecular, cellular and tissues scales and organisms. This includes contributions directed towards understanding biochemical and biophysical mechanisms, structure-function relationships with respect to basic cell and tissue functions, development, development/evolution relationship, morphogenesis, stem cell biology, cell biology of disease, plant cell biology, as well as contributions directed toward understanding integrated processes at the organelles, cell and tissue levels. Contributions using approaches such as high resolution imaging, live imaging, quantitative cell biology and integrated biology; as well as those using innovative genetic and epigenetic technologies, ex-vivo tissue engineering, cellular, tissue and integrated functional analysis, and quantitative biology and modeling to demonstrate original biological principles are encouraged.
×
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:604180095
Book学术官方微信