A Four-Dimensional Organoid System to Visualize Cancer Cell Vascular Invasion

SIMPLE SUMMARY: Using vascular organoid culture with collagen microfiber, we have established a method for culturing organoids that recapitulates the vascular invasion process of cancer cells. This culture model made it possible to four-dimensionally evaluate the dynamics of cancer cells infiltrating into blood vessels. ABSTRACT: Vascular invasion of cancer is a critical step in cancer progression, but no drug has been developed to inhibit vascular invasion. To achieve the eradication of cancer metastasis, elucidation of the mechanism for vascular invasion and the development of innovative treatment methods are required. Here, a simple and reproducible vascular invasion model is established using a vascular organoid culture in a fibrin gel with collagen microfibers. Using this model, it was possible to observe and evaluate the cell dynamics and histological positional relationship of invasive cancer cells in four dimensions. Cancer-derived exosomes promoted the vascular invasion of cancer cells and loosened tight junctions in the vascular endothelium. As a new evaluation method, research using this vascular invasion mimic model will be advanced, and applications to the evaluation of the vascular invasion suppression effect of a drug are expected.