Biology subjects

Suehiro, J.-i.

Publications and source records attributed to Suehiro, J.-i..

2 recordsLinked to original sources

bioRxiv2024

Tumor-microvessel on-a-chip reveals sequential intravasation cascade of cancer cell clusters

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-{beta} (TGF-{beta}) 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.

cancer biology↗

bioRxiv2023

Endothelial tissue remodeling induced by intraluminal pressure enhances paracellular solute transport

The endothelial layers of the microvasculature regulate the transport of solutes to the surrounding tissues. It remains unclear how this barrier function is affected by blood flow-induced intraluminal pressure. Using a 3D microvessel model, we compare the transport of macromolecules through endothelial tissues at mechanical rest or with intraluminal pressure, and correlate these data with electron microscopy of endothelial junctions. Upon application of an intraluminal pressure of 100 Pa, we demonstrate that the flow through the tissue increases by 135%. This increase is associated with a 25% expansion of microvessel diameter, which leads to tissue remodeling and thinning of the paracellular junctions. We recapitulate these data with the deformable monopore model, in which the increase in paracellular transport is explained by the augmentation of the diffusion rate across thinned junctions under mechanical stress. We therefore suggest that the deformation of microvasculatures contributes to regulate their barrier function.

biophysics↗