RT Journal Article SR Electronic T1 Tumor-microvessel on-a-chip reveals sequential intravasation cascade of cancer cell clusters JF bioRxiv FD Cold Spring Harbor Laboratory SP 2024.02.28.582606 DO 10.1101/2024.02.28.582606 A1 Ikeda, Yukinori A1 Suehiro, Jun-ichi A1 Oshima, Hiroko A1 Kok, Sau Yee A1 Takahashi, Kazuki A1 Sakurai, Hiroyuki A1 Watabe, Tetsuro A1 Oshima, Masanobu A1 Matsunaga, Yukiko T. YR 2024 UL http://biorxiv.org/content/early/2024/03/04/2024.02.28.582606.abstract AB 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 CTC clusters are released from primary tumors beyond blood vessel barriers remain unclear. In this study, a three-dimensional (3D) in vitro culture system is 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 in the collagen gel, vessel co-option, and the release of CTC clusters as one of cluster invasion manners yet reported previously. In addition, our results show that both transforming growth factor-β (TGF-β) expression in tumor cells and subsequent induction of activin expression in endothelium are essential for tumor cell intravasation accompanied 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 CTC clusters.Competing Interest StatementThe authors have declared no competing interest.