建立体外器官型3D外阴模型,研究肿瘤-基质相互作用及药物疗效。

IF 6.6 2区 医学 Q1 Medicine Cellular Oncology Pub Date : 2024-06-01 Epub Date: 2023-12-07 DOI:10.1007/s13402-023-00902-w
Shidi Wu, Bertine W Huisman, Marion H Rietveld, Robert Rissmann, Maarten H Vermeer, Mariette I E van Poelgeest, Abdoelwaheb El Ghalbzouri
{"title":"建立体外器官型3D外阴模型,研究肿瘤-基质相互作用及药物疗效。","authors":"Shidi Wu, Bertine W Huisman, Marion H Rietveld, Robert Rissmann, Maarten H Vermeer, Mariette I E van Poelgeest, Abdoelwaheb El Ghalbzouri","doi":"10.1007/s13402-023-00902-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Vulvar squamous cell carcinoma (VSCC) is a rare disease with a poor prognosis. To date, there's no proper in vitro modeling system for VSCC to study its pathogenesis or for drug evaluation.</p><p><strong>Methods: </strong>We established healthy vulvar (HV)- and VSCC-like 3D full thickness models (FTMs) to observe the tumor-stroma interaction and their applicability for chemotherapeutic efficacy examination. VSCC-FTMs were developed by seeding VSCC tumor cell lines (A431 and HTB117) onto dermal matrices harboring two NF subtypes namely papillary fibroblasts (PFs) and reticular fibroblasts (RFs), or cancer-associated fibroblasts (CAFs) while HV-FTMs were constructed with primary keratinocytes and fibroblasts isolated from HV tissues.</p><p><strong>Results: </strong>HV-FTMs highly resembled HV tissues in terms of epidermal morphogenesis, basement membrane formation and collagen deposition. When the dermal compartment shifted from PFs to RFs or CAFs in VSCC-FTMs, tumor cells demonstrated more proliferation, EMT induction and stemness. In contrast to PFs, RFs started to lose their phenotype and express robust CAF-markers α-SMA and COL11A1 under tumor cell signaling induction, indicating a favored 'RF-to-CAF' transition in VSCC tumor microenvironment (TME). Additionally, chemotherapeutic treatment with carboplatin and paclitaxel resulted in a significant reduction in tumor-load and invasion in VSCC-FTMs.</p><p><strong>Conclusion: </strong>We successfully developed in vitro 3D vulvar models mimicking both healthy and tumorous conditions which serve as a promising tool for vulvar drug screening programs. Moreover, healthy fibroblasts demonstrate heterogeneity in terms of CAF-activation in VSCC TME which brings insights in the future development of novel CAF-based therapeutic strategies in VSCC.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":6.6000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The development of in vitro organotypic 3D vulvar models to study tumor-stroma interaction and drug efficacy.\",\"authors\":\"Shidi Wu, Bertine W Huisman, Marion H Rietveld, Robert Rissmann, Maarten H Vermeer, Mariette I E van Poelgeest, Abdoelwaheb El Ghalbzouri\",\"doi\":\"10.1007/s13402-023-00902-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Vulvar squamous cell carcinoma (VSCC) is a rare disease with a poor prognosis. To date, there's no proper in vitro modeling system for VSCC to study its pathogenesis or for drug evaluation.</p><p><strong>Methods: </strong>We established healthy vulvar (HV)- and VSCC-like 3D full thickness models (FTMs) to observe the tumor-stroma interaction and their applicability for chemotherapeutic efficacy examination. VSCC-FTMs were developed by seeding VSCC tumor cell lines (A431 and HTB117) onto dermal matrices harboring two NF subtypes namely papillary fibroblasts (PFs) and reticular fibroblasts (RFs), or cancer-associated fibroblasts (CAFs) while HV-FTMs were constructed with primary keratinocytes and fibroblasts isolated from HV tissues.</p><p><strong>Results: </strong>HV-FTMs highly resembled HV tissues in terms of epidermal morphogenesis, basement membrane formation and collagen deposition. When the dermal compartment shifted from PFs to RFs or CAFs in VSCC-FTMs, tumor cells demonstrated more proliferation, EMT induction and stemness. In contrast to PFs, RFs started to lose their phenotype and express robust CAF-markers α-SMA and COL11A1 under tumor cell signaling induction, indicating a favored 'RF-to-CAF' transition in VSCC tumor microenvironment (TME). Additionally, chemotherapeutic treatment with carboplatin and paclitaxel resulted in a significant reduction in tumor-load and invasion in VSCC-FTMs.</p><p><strong>Conclusion: </strong>We successfully developed in vitro 3D vulvar models mimicking both healthy and tumorous conditions which serve as a promising tool for vulvar drug screening programs. Moreover, healthy fibroblasts demonstrate heterogeneity in terms of CAF-activation in VSCC TME which brings insights in the future development of novel CAF-based therapeutic strategies in VSCC.</p>\",\"PeriodicalId\":9690,\"journal\":{\"name\":\"Cellular Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.6000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cellular Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13402-023-00902-w\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/12/7 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13402-023-00902-w","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/12/7 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0

摘要

背景:外阴鳞状细胞癌(VSCC)是一种罕见的疾病,预后较差。到目前为止,还没有合适的体外造模系统来研究VSCC的发病机制或进行药物评价。方法:建立健康外阴(HV)样和vscc样三维全层模型(FTMs),观察肿瘤与间质相互作用及其在化疗疗效检验中的适用性。VSCC- ftms是通过将VSCC肿瘤细胞系(A431和HTB117)播种到含有两种NF亚型(乳头状成纤维细胞(PFs)和网状成纤维细胞(RFs)或癌症相关成纤维细胞(CAFs)的真皮基质上培育而成的,而HV- ftms是用从HV组织中分离的原代角质形成细胞和成纤维细胞构建的。结果:HV- ftms在表皮形态发生、基底膜形成和胶原沉积等方面与HV组织高度相似。在VSCC-FTMs中,当真皮隔室从PFs转移到RFs或CAFs时,肿瘤细胞表现出更多的增殖、EMT诱导和干细胞性。与PFs相比,在肿瘤细胞信号传导诱导下,RFs开始失去其表型并表达强大的caf标记α-SMA和COL11A1,这表明VSCC肿瘤微环境(TME)中更倾向于“rf到caf”的转变。此外,卡铂和紫杉醇化疗可显著降低VSCC-FTMs的肿瘤负荷和侵袭。结论:我们成功地建立了模拟健康和肿瘤情况的体外3D外阴模型,为外阴药物筛选提供了一个有前途的工具。此外,健康成纤维细胞在VSCC TME中cafa活化方面表现出异质性,这为未来开发新的基于cafa的VSCC治疗策略提供了见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

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
The development of in vitro organotypic 3D vulvar models to study tumor-stroma interaction and drug efficacy.

Background: Vulvar squamous cell carcinoma (VSCC) is a rare disease with a poor prognosis. To date, there's no proper in vitro modeling system for VSCC to study its pathogenesis or for drug evaluation.

Methods: We established healthy vulvar (HV)- and VSCC-like 3D full thickness models (FTMs) to observe the tumor-stroma interaction and their applicability for chemotherapeutic efficacy examination. VSCC-FTMs were developed by seeding VSCC tumor cell lines (A431 and HTB117) onto dermal matrices harboring two NF subtypes namely papillary fibroblasts (PFs) and reticular fibroblasts (RFs), or cancer-associated fibroblasts (CAFs) while HV-FTMs were constructed with primary keratinocytes and fibroblasts isolated from HV tissues.

Results: HV-FTMs highly resembled HV tissues in terms of epidermal morphogenesis, basement membrane formation and collagen deposition. When the dermal compartment shifted from PFs to RFs or CAFs in VSCC-FTMs, tumor cells demonstrated more proliferation, EMT induction and stemness. In contrast to PFs, RFs started to lose their phenotype and express robust CAF-markers α-SMA and COL11A1 under tumor cell signaling induction, indicating a favored 'RF-to-CAF' transition in VSCC tumor microenvironment (TME). Additionally, chemotherapeutic treatment with carboplatin and paclitaxel resulted in a significant reduction in tumor-load and invasion in VSCC-FTMs.

Conclusion: We successfully developed in vitro 3D vulvar models mimicking both healthy and tumorous conditions which serve as a promising tool for vulvar drug screening programs. Moreover, healthy fibroblasts demonstrate heterogeneity in terms of CAF-activation in VSCC TME which brings insights in the future development of novel CAF-based therapeutic strategies in VSCC.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Cellular Oncology
Cellular Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
10.40
自引率
1.50%
发文量
0
审稿时长
16 weeks
期刊介绍: The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.
期刊最新文献
Cell death in glioblastoma and the central nervous system. SUMOylation regulates the aggressiveness of breast cancer-associated fibroblasts. Retraction Note: The autocrine glycosylated-GREM1 interacts with TGFB1 to suppress TGFβ/BMP/SMAD-mediated EMT partially by inhibiting MYL9 transactivation in urinary carcinoma. USP28 promotes tumor progression and glycolysis by stabilizing PKM2/Hif1-α in cholangiocarcinoma. BCAT1 contributes to the development of TKI-resistant CML.
×
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