Mathematical Model of the Effect of Interstitial Fluid Pressure on Angiogenic Behavior in Solid Tumors

We present a mathematical model for the concentrations of proangiogenic and antiangiogenic growth factors, and their resulting balance/imbalance, in host and tumor tissue. In addition to production, diffusion, and degradation of these angiogenic growth factors (AGFs), we include interstitial convection to study the locally destabilizing effects of interstitial fluid pressure (IFP) on the activity of these factors. The molecular sizes of representative AGFs and the outward flow of interstitial fluid in tumors suggest that convection is a significant mode of transport for these molecules. The results of our modeling approach suggest that changes in the physiological parameters that determine interstitial fluid pressure have as profound an impact on tumor angiogenesis as those parameters controlling production, diffusion, and degradation of AGFs. This model has predictive potential for determining the angiogenic behavior of solid tumors and the effects of cytotoxic and antiangiogenic therapies on tumor angiogenesis.