Vascularized tumor on a microfluidic chip to study mechanisms promoting tumor neovascularization and vascular targeted therapies

Abstract

AbstractThe cascade of events leading to tumor formation includes induction of a tumor supporting neovasculature as a primary hallmark of cancer. Developing vasculature is difficult to evaluatein vivobut can be captured using microfluidic chip technology and patient derived cells. Herein, we established anon chipapproach to investigate the mechanisms promoting tumor vascularization and vascular targeted therapies via co-culture of metastatic renal cell carcinoma spheroids and endothelial cells in a 3D environment. Our model permitted real-time, high-resolution observation and assessment of tumor-induced angiogenesis, where endothelial cells sprout towards the tumor and mimic a vascular network. Bevacizumab, an angiogenic inhibitor, disrupted interactions between vessels and tumors, destroying the vascular network. Theon chipapproach enabled assessment of endothelial cell biology, vessel’s functionality, drug delivery, and molecular expression of PSMA. Finally, observations in the vascularized tumoron chippermitted direct and conclusive quantification of this therapy in weeks as opposed to months in a comparable animal model.TeaserVascularized tumor on microfluidic chip provides opportunity to study targeted therapies and improves preclinical drug discovery.