Tumor growth and development relies on rapid formation on new blood vessels, i.e. angiogenesis, to keep up with increasing demands for nutrients and oxygen. Due to an imbalance between pro- and anti-angiogenic factors, and rapid angiogenesis, an aberrant vascular morphology develops¹, which is characteristic for each specific tumor type². This aberrant morphology is also associated with pathological hemodynamics³. However, a mechanistic understanding of the link between compromised hemodynamics and aberrant tumor endothelial biology is lacking. Moreover, the molecular mechanisms underlying the different vascular morphology between different tumor types, is also unknown.

This knowledge gap is due in part to a lack of experimental systems that enable precise and controlled investigation of tumor hemodynamics and their connection to aberrant tumor vascular morphology. In vivo, there is little or no experimental control over blood flow and blood pressure in the tumor vasculature and changes in nutrient exchange are coupled with mechanical effects of blood flow. Also, current commercially available in vitro models require culturing of cells on flat, stiff substrates, which does not recapitulate the complexity of aberrant tumor vascular morphology growing in three-dimensional tissue⁴. On the other hand, results obtained from in vitro experimental systems need to be validated in vivo.

The proposed project will establish a new collaboration between the group of William J Polacheck from the University of North Carolina at Chapel Hill (UNC Chapel Hill | NC State, US) and the Department of Experimental Oncology (Institute of Oncology Ljubljana, Slovenia). The US group has extensive experience with developing perfusable three-dimensional biomimetic vascular models that they have successfully used to investigate molecular and mechanical aspects of non-tumor vascular biology⁴. However, they have not yet applied them to investigate the behavior of endothelial cells in tumor-like microenvironment. On the other hand, the Slovenian group has extensive expertise with in vivo intravital microscopy and has successfully used it to follow the developing tumor vasculature⁵. The collaboration between the two groups would therefore present a unique possibility to investigate tumor hemodynamics and their connection to aberrant tumor vascular morphology in a precise and controlled environment in vitro and then validate the findings with intravital microscopy in vivo.