title: Modeling the effects of vasculature evolution on early brain tumor growth.
abstract: Mathematical modeling of both tumor growth and angiogenesis have been active areas of research for the past several decades. Such models can be classified into one of two categories: those that analyze the remodeling of the vasculature while ignoring changes in the tumor mass, and those that predict tumor expansion in the presence of a non-evolving vasculature. However, it is well accepted that vasculature remodeling and tumor growth strongly depend on one another. For this reason, we have developed a two-dimensional hybrid cellular automaton model of early brain tumor growth that couples the remodeling of the microvasculature with the evolution of the tumor mass. A system of reaction-diffusion equations has been developed to track the concentration of vascular endothelial growth factor (VEGF), Ang-1, Ang-2, their receptors and their complexes in space and time. The properties of the vasculature and hence of each cell are determined by the relative concentrations of these key angiogenic factors. The model exhibits an angiogenic switch consistent with experimental observations on the upregulation of angiogenesis. Particularly, we show that if the pathways that produce and respond to VEGF and the angiopoietins are properly functioning, angiogenesis is initiated and a tumor can grow to a macroscopic size. However, if the VEGF pathway is inhibited, angiogenesis does not occur and tumor growth is thwarted beyond 1-2mm in size. Furthermore, we show that tumor expansion can occur in well-vascularized environments even when angiogenesis is inhibited, suggesting that anti-angiogenic therapies may not be sufficient to eliminate a population of actively dividing malignant cells.
authors.affiliation: Program in Applied and Computational Mathematics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Jana L
authors.initials: JL
authors.lastname: Gevertz
authors.forename: Salvatore
authors.initials: S
authors.lastname: Torquato
mesh_terms: D000465:Algorithms; D042682:Angiopoietins / Q000502:physiology; D001932:Brain Neoplasms / Q000098:blood supply* / Q000473:pathology; D049109:Cell Proliferation; D018450:Disease Progression; D025461:Feedback, Physiological; D005909:Glioblastoma / Q000098:blood supply* / Q000473:pathology; D006801:Humans; D008833:Microcirculation; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D042682:Angiopoietins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A