Establishment and drug resistance characterization of paired organoids using human primary colorectal cancer and matched tumor deposit specimens.

IF 3.4 3区 生物学 Q3 CELL BIOLOGY
Jiao Deng, Jerry H Qin, Xiaolan Li, Deding Tao, Yongdong Feng
{"title":"Establishment and drug resistance characterization of paired organoids using human primary colorectal cancer and matched tumor deposit specimens.","authors":"Jiao Deng, Jerry H Qin, Xiaolan Li, Deding Tao, Yongdong Feng","doi":"10.1007/s13577-024-01139-x","DOIUrl":null,"url":null,"abstract":"<p><p>Tumor deposits (TDs) represent a specific form tumor metastasis observed in colorectal cancer (CRC). The lack of successfully established cell lines for TDs, as well as the molecular mechanisms by which TDs occur remain largely unknown. Here, we established paired CRC organoids, including a human primary cancer organoid and its TD organoid, from a 46-year-old male patient with CRC. Further analysis revealed that, compared with primary tumor-derived cells, TD-derived cells exhibited enhanced proliferative, invasive and metastatic capabilities, and increased expression of stemness-related proteins. Furthermore, the present findings also demonstrated that TD-derived cells were more resistant to oxaliplatin or 5-FU. Transcriptomic profiling and qPCR revealed that TD-derived cells exhibited more alterations in fatty acid metabolism signaling and enhanced lipid synthesis ability compared to primary tumor-derived cells. Inhibition of lipid synthesis markedly decreased resistance to oxaliplatin in TD-derived cells. Taken together, the paired organoids established using CRC primary tumor and its TD specimens will provide valuable tools to study tumorigenicity, metastasis and chemoresistance in CRC. Notably, these models will provide novel insights to study tumor heterogeneity and lipid metabolism in CRC.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534897/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s13577-024-01139-x","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Tumor deposits (TDs) represent a specific form tumor metastasis observed in colorectal cancer (CRC). The lack of successfully established cell lines for TDs, as well as the molecular mechanisms by which TDs occur remain largely unknown. Here, we established paired CRC organoids, including a human primary cancer organoid and its TD organoid, from a 46-year-old male patient with CRC. Further analysis revealed that, compared with primary tumor-derived cells, TD-derived cells exhibited enhanced proliferative, invasive and metastatic capabilities, and increased expression of stemness-related proteins. Furthermore, the present findings also demonstrated that TD-derived cells were more resistant to oxaliplatin or 5-FU. Transcriptomic profiling and qPCR revealed that TD-derived cells exhibited more alterations in fatty acid metabolism signaling and enhanced lipid synthesis ability compared to primary tumor-derived cells. Inhibition of lipid synthesis markedly decreased resistance to oxaliplatin in TD-derived cells. Taken together, the paired organoids established using CRC primary tumor and its TD specimens will provide valuable tools to study tumorigenicity, metastasis and chemoresistance in CRC. Notably, these models will provide novel insights to study tumor heterogeneity and lipid metabolism in CRC.

利用人体原发性结直肠癌和匹配的肿瘤沉积标本建立配对有机体并确定其耐药性特征。
肿瘤沉积(TDs)是结直肠癌(CRC)中一种特殊的肿瘤转移形式。由于缺乏成功建立的 TDs 细胞系,TDs 发生的分子机制在很大程度上仍然未知。在这里,我们从一名 46 岁的男性 CRC 患者身上建立了成对的 CRC 有机体,包括一个人类原发性癌症有机体及其 TD 有机体。进一步的分析表明,与原发肿瘤衍生细胞相比,TD衍生细胞具有更强的增殖、侵袭和转移能力,干性相关蛋白的表达也有所增加。此外,本研究结果还表明,TD 衍生细胞对奥沙利铂或 5-FU 的耐药性更强。转录组分析和 qPCR 显示,与原发肿瘤衍生细胞相比,TD 衍生细胞在脂肪酸代谢信号转导方面发生了更多改变,脂质合成能力增强。抑制脂质合成可显著降低 TD 衍生细胞对奥沙利铂的耐药性。总而言之,利用 CRC 原发肿瘤及其 TD 标本建立的配对有机体将为研究 CRC 的致瘤性、转移性和化疗耐药性提供有价值的工具。值得注意的是,这些模型将为研究 CRC 的肿瘤异质性和脂质代谢提供新的见解。
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
Human Cell
Human Cell CELL BIOLOGY-
CiteScore
5.90
自引率
2.30%
发文量
176
审稿时长
4.5 months
期刊介绍: Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well. Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format. Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.
×
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