Model of vascular desmoplastic multispecies tumor growth.

We present a three-dimensional nonlinear tumor growth model composed of heterogeneous cell types in a multicomponent-multispecies system, including viable, dead, healthy host, and extra-cellular matrix (ECM) tissue species. The model includes the capability for abnormal ECM dynamics noted in tumor development, as exemplified by pancreatic ductal adenocarcinoma, including dense desmoplasia typically characterized by a significant increase of interstitial connective tissue. An elastic energy is implemented to provide elasticity to the connective tissue. Cancer-associated fibroblasts (myofibroblasts) are modeled as key contributors to this ECM remodeling. The tumor growth is driven by growth factors released by these stromal cells as well as by oxygen and glucose provided by blood vasculature which along with lymphatics are stimulated to proliferate in and around the tumor based on pro-angiogenic factors released by hypoxic tissue regions. Cellular metabolic processes are simulated, including respiration and glycolysis with lactate fermentation. The bicarbonate buffering system is included for cellular pH regulation. This model system may be of use to simulate the complex interactions between tumor and stromal cells as well as the associated ECM and vascular remodeling that typically characterize malignant cancers notorious for poor therapeutic response.