Nano Biomedicine
ORIGINAL ARTICLE

Spatiotemporal Observation Reveals Metastatic Tumor-driven Vascular Remodeling as a Potential Route to Polyclonal Colonization

Yukinori IKEDA1, 2, Hiroko OSHIMA3, 4, Sau Yee KOK3, Masanobu OSHIMA3, 4, and Yukiko T. MATSUNAGA1, 2

1Institute of Industrial Science, The University of Tokyo, Tokyo, Japan
2Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, Japan
3Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
4WPI Nano Life Science Institute, Kanazawa University, Kanazawa, Japan
Nano Biomed 2024; 16(1):19-27, (Jun 30, Nano Biomedicine)
Synopsis
Polyclonal metastasis, which arises from clusters of circulating tumor cells, promotes metastasis development and has become a major target of metastasis inhibition. Mouse experiments have clearly verified that nonmetastatic and metastatic tumors coexist and form metastatic nests, but the detailed mechanism of extravasation remains unclear. We established a three-dimensional tumor microvessel model to investigate extravasation between nonmetastatic tumors, metastatic tumors, and mosaic tumor organoids in a mixed state by time-lapse imaging and to determine the sequential steps of the extravasation of tumor cells via vascular remodeling. This comparison revealed a new concept of extravascular invasion via vascular remodeling in metastatic carcinoma. Furthermore, the involvement of liver host cells, the hepatic stellate cells, demonstrated an interaction with metastatic cells to facilitate metastatic foci formation. Moreover, Adam28 was highly expressed exclusively in metastatic tumor cells, suggesting its involvement in vascular remodeling. These results demonstrate the ability of metastatic tumor cells for extravasation in polyclonal metastasis, which may lead to the development of new therapeutic targets.

Key words: polyclonal metastasis, vascular microenvironment, extravasation, microvessel model, tumor organoid


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DOI : "https://doi.org/10.11344/nano.16.19"

J-stage : Ikeda Y, Oshima H, Kok SY, Oshima M, Matsunaga YT. Spatiotemporal observation reveals metastatic tumor-driven vascular remodeling as a potential route to polyclonal colonization. Nano Biomed 2024; 16: 19-27.