肿瘤微血管芯片揭示了癌细胞簇内渗的机制

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-04-24 DOI:10.1016/j.isci.2025.112517

Yukinori Ikeda , Makoto Kondo , Jun-ichi Suehiro , Hiroko Oshima , Sau Yee Kok , Kazuki Takahashi , Joris Pauty , Dong Wang , Hiroyuki Sakurai , Tetsuro Watabe , Masanobu Oshima , Yukiko T. Matsunaga

{"title":"肿瘤微血管芯片揭示了癌细胞簇内渗的机制","authors":"Yukinori Ikeda , Makoto Kondo , Jun-ichi Suehiro , Hiroko Oshima , Sau Yee Kok , Kazuki Takahashi , Joris Pauty , Dong Wang , Hiroyuki Sakurai , Tetsuro Watabe , Masanobu Oshima , Yukiko T. Matsunaga","doi":"10.1016/j.isci.2025.112517","DOIUrl":null,"url":null,"abstract":"<div><div>Circulating tumor cell (CTC) clusters are often detected in blood samples of patients with high-grade tumor and are associated with tumor metastasis and poor prognosis. However, the underlying mechanisms by which cancer cell clusters are released from primary tumors beyond blood vessel barriers remain unclear. In this study, a three-dimensional (3D) <em>in vitro</em> culture system was developed to visualize tumor intravasation by positioning tumor organoids with distinct genetic backgrounds to surround microvessels. We visualized tumor intravasation in a cluster unit, including collective migration toward microvessels, vessel co-option, and the release of CTC clusters—an invasion mechanism not previously reported. Furthermore, elevated levels of transforming growth factor β (TGF-β) and activin expression in endothelial cells within the coculture microenvironment were pivotal for facilitating tumor cell intravasation, which was associated with endothelial-to-mesenchymal transition (EndoMT) in microvessels. Our 3D <em>in vitro</em> system can be used to develop therapeutic strategies for tumor metastasis by targeting the release of CTC clusters.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112517"},"PeriodicalIF":4.6000,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A tumor-microvessel on-a-chip reveals a mechanism for cancer cell cluster intravasation\",\"authors\":\"Yukinori Ikeda , Makoto Kondo , Jun-ichi Suehiro , Hiroko Oshima , Sau Yee Kok , Kazuki Takahashi , Joris Pauty , Dong Wang , Hiroyuki Sakurai , Tetsuro Watabe , Masanobu Oshima , Yukiko T. Matsunaga\",\"doi\":\"10.1016/j.isci.2025.112517\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Circulating tumor cell (CTC) clusters are often detected in blood samples of patients with high-grade tumor and are associated with tumor metastasis and poor prognosis. However, the underlying mechanisms by which cancer cell clusters are released from primary tumors beyond blood vessel barriers remain unclear. In this study, a three-dimensional (3D) <em>in vitro</em> culture system was developed to visualize tumor intravasation by positioning tumor organoids with distinct genetic backgrounds to surround microvessels. We visualized tumor intravasation in a cluster unit, including collective migration toward microvessels, vessel co-option, and the release of CTC clusters—an invasion mechanism not previously reported. Furthermore, elevated levels of transforming growth factor β (TGF-β) and activin expression in endothelial cells within the coculture microenvironment were pivotal for facilitating tumor cell intravasation, which was associated with endothelial-to-mesenchymal transition (EndoMT) in microvessels. Our 3D <em>in vitro</em> system can be used to develop therapeutic strategies for tumor metastasis by targeting the release of CTC clusters.</div></div>\",\"PeriodicalId\":342,\"journal\":{\"name\":\"iScience\",\"volume\":\"28 6\",\"pages\":\"Article 112517\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-04-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"iScience\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2589004225007783\",\"RegionNum\":2,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"iScience","FirstCategoryId":"103","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2589004225007783","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

摘要

循环肿瘤细胞（CTC）簇经常在高级别肿瘤患者的血液样本中检测到，并与肿瘤转移和预后不良有关。然而，癌细胞簇从原发肿瘤中释放出血管屏障之外的潜在机制尚不清楚。在这项研究中，我们开发了一个三维（3D）体外培养系统，通过定位具有不同遗传背景的肿瘤类器官来观察肿瘤在微血管周围的内渗。我们可视化了肿瘤在集群单元中的内渗，包括向微血管的集体迁移、血管的选择和CTC集群的释放——这是一种以前未报道的侵袭机制。此外，在共培养微环境中，内皮细胞中转化生长因子β (TGF-β)和激活素表达水平的升高是促进肿瘤细胞内渗的关键，这与微血管中内皮到间充质转化（EndoMT）有关。我们的3D体外系统可以通过靶向CTC簇的释放来开发肿瘤转移的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

A tumor-microvessel on-a-chip reveals a mechanism for cancer cell cluster intravasation

Circulating tumor cell (CTC) clusters are often detected in blood samples of patients with high-grade tumor and are associated with tumor metastasis and poor prognosis. However, the underlying mechanisms by which cancer cell clusters are released from primary tumors beyond blood vessel barriers remain unclear. In this study, a three-dimensional (3D) in vitro culture system was developed to visualize tumor intravasation by positioning tumor organoids with distinct genetic backgrounds to surround microvessels. We visualized tumor intravasation in a cluster unit, including collective migration toward microvessels, vessel co-option, and the release of CTC clusters—an invasion mechanism not previously reported. Furthermore, elevated levels of transforming growth factor β (TGF-β) and activin expression in endothelial cells within the coculture microenvironment were pivotal for facilitating tumor cell intravasation, which was associated with endothelial-to-mesenchymal transition (EndoMT) in microvessels. Our 3D in vitro system can be used to develop therapeutic strategies for tumor metastasis by targeting the release of CTC clusters.

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

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

期刊介绍： Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results. We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.