{"title":"Lung tumor organoids migrate as cell clusters containing cancer stem cells under hypoxic condition","authors":"Yanjiao Li, Jiarong Zou, Yanhua Fang, Jianing Zuo, Ruoyu Wang, 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.
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.