Advanced Drug Screening Platform Utilizing Capillary and Artery Models Based on Tumor-Vessel Interactions

One of the hallmarks of tumors is angiogenesis, which involves forming new blood vessels around the tumor to provide it with oxygen and nutrients, thus supporting tumor growth and metastasis. In this study, we created a tumor-vessel spheroid model that can be used for high-throughput screening using microwells. The cancer spheroid model is an inverted version of a native environment with glioblastoma (GBM) at the center, the artery model is human smooth muscle cells (SMCs) and human umbilical vein endothelial cells (HUVECs) surrounding the GBM, and the capillary model is surrounded by a layer of HUVECs only. We observed differential characteristics in the interaction between tumors and these blood vessels through junction markers and revealed strong expression of platelet endothelial cell adhesion molecule (PECAM) with the interaction of GBM and HUVECs. Comparisons with tumors derived from different organs and cytokine array analysis revealed expression of PECAM was brain-specific. Anti-cancer drug testing with doxorubicin and bevacizumab showed an increase in PECAM-associated proteins and drug resistance cytokines, and that adding flow to the drug environment increased viability compared to static conditions, further confirming that our model mimics the native model well. This demonstrates that our model shows that PECAM influences the interaction of tumors and blood vessels, advancing our understanding of the interaction between different tumor types and adjacent blood vessels and could serve as a platform for personalized devices using patient-derived cells.