Flow‐Induced Structural Adaptation of Tumor Vasculature by Selective Micro‐Laser Ablation

Abstract

The effects of anti‐angiogenesis therapy on tumor vasculature are transient, and the exact mechanisms of vessel remodeling are not known. Here we developed experimental and theoretical models of tumor vascular remodeling for customizing the dose and timing of vessel‐targeted drugs. We used a multiphoton laser to interrupt vessel segments downstream from a bifurcation and observed remodeling in the adjacent branches in normal skin vasculature and AK4.4 pancreatic tumors implanted in the mouse dorsal skin fold chamber. We assessed blood flow and cellular dynamics using fluorescence stereomicroscopy and optical frequency‐domain imaging. The theoretical simulation of the vascular network dynamics is based on a previous network model developed by Gruionu et al (Am J Physiol, 2005). A finite element model was used to simulate oxygen and nutrient delivery in the surrounding tissue. The laser microsurgery caused significant remodeling in both arterial (mean: 151%, max: 229%) and venous (mean: 153%, max: 581%) sides of the circulation. The predictions of the model showed good correlation with the observed changes in the dorsal skinfold chamber. The models will help us define the contribution of local stimuli to remodeling of tumor vascular beds and generate predictions for altering tumor blood flow and development of future therapies. Supported by NIH R01CA149285 and CNCS (Romania) PN‐II‐ID‐PCE‐2011–3‐0664.