A tumor-microvessel on-a-chip reveals a mechanism for cancer cell cluster intravasation
Summary: 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 barr...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225007783 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yukinori Ikeda |
| collection | DOAJ |
| description | Summary: 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. |
| format | Article |
| id | doaj-art-3726bf79b32347f2b7b706c3fccba8ea |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-3726bf79b32347f2b7b706c3fccba8ea2025-08-20T03:07:11ZengElsevieriScience2589-00422025-06-0128611251710.1016/j.isci.2025.112517A tumor-microvessel on-a-chip reveals a mechanism for cancer cell cluster intravasationYukinori Ikeda0Makoto Kondo1Jun-ichi Suehiro2Hiroko Oshima3Sau Yee Kok4Kazuki Takahashi5Joris Pauty6Dong Wang7Hiroyuki Sakurai8Tetsuro Watabe9Masanobu Oshima10Yukiko T. Matsunaga11Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan; Department of Bioengineering, School of Engineering, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, JapanInstitute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan; Department of Bioengineering, School of Engineering, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, JapanDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka, Tokyo 181-8611, JapanDivision of Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, JapanDivision of Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, JapanInstitute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan; Department of Biochemistry, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, JapanInstitute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, JapanDivision of Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan; WPI Nano Life Science Institute, Kanazawa University, Kanazawa 920-1192, JapanDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka, Tokyo 181-8611, JapanDepartment of Biochemistry, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, JapanDivision of Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan; WPI Nano Life Science Institute, Kanazawa University, Kanazawa 920-1192, Japan; Corresponding authorInstitute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan; Department of Bioengineering, School of Engineering, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004225007783MicroenvironmentBiological sciencesBiotechnologyCell biologyCancer |
| spellingShingle | 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 A tumor-microvessel on-a-chip reveals a mechanism for cancer cell cluster intravasation iScience Microenvironment Biological sciences Biotechnology Cell biology Cancer |
| title | A tumor-microvessel on-a-chip reveals a mechanism for cancer cell cluster intravasation |
| title_full | A tumor-microvessel on-a-chip reveals a mechanism for cancer cell cluster intravasation |
| title_fullStr | A tumor-microvessel on-a-chip reveals a mechanism for cancer cell cluster intravasation |
| title_full_unstemmed | A tumor-microvessel on-a-chip reveals a mechanism for cancer cell cluster intravasation |
| title_short | A tumor-microvessel on-a-chip reveals a mechanism for cancer cell cluster intravasation |
| title_sort | tumor microvessel on a chip reveals a mechanism for cancer cell cluster intravasation |
| topic | Microenvironment Biological sciences Biotechnology Cell biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225007783 |
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