Combined Influence of Nutrient Supply Level and Tissue Mechanical Properties on Benign Tumor Growth as Revealed by Mathematical Modeling

Abstract

A continuous mathematical model of non-invasive avascular tumor growth in tissue is presented. The model considers tissue as a biphasic material, comprised of a solid matrix and interstitial fluid. The convective motion of tissue elements happens due to the gradients of stress, which change as a result of tumor cells proliferation and death. The model accounts for glucose as the crucial nutrient, supplied from the normal tissue, and can reproduce both diffusion-limited and stress-limited tumor growth. Approximate tumor growth curves are obtained semi-analytically in the limit of infinite tissue hydraulic conductivity, which implies instantaneous equalization of arising stress gradients. These growth curves correspond well to the numerical solutions and represent classical sigmoidal curves with a short initial exponential phase, subsequent almost linear growth phase and a phase with growth deceleration, in which tumor tends to reach its maximum volume. The influence of two model parameters on tumor growth curves is investigated: tissue hydraulic conductivity, which links the values of stress gradient and convective velocity of tissue phases, and tumor nutrient supply level, which corresponds to different permeability and surface area density of capillaries in the normal tissue that surrounds the tumor. In particular, it is demonstrated, that sufficiently low tissue hydraulic conductivity (intrinsic, e.g., to tumors arising from connective tissue) and sufficiently high nutrient supply can lead to formation of giant benign tumors, reaching tens of centimeters in diameter, which are indeed observed clinically.