A computational investigation of the role of angiogenic inhibitors in tumor-induced angiogenesis

Angiogenesis, the formation of new blood vessels from preexisting vasculature, is an essential component of tumor growth. Without this, solid tumors are nutrient limited and cannot grow more than 1-2 mm in diameter and the tumor mass cannot contain more than 10⁵-10⁶ cells. The recent discovery of angiogenic inhibitors has revolutionized the field making anti-angiogenic treatment one of the most potent therapies for cancer. Despite this progress, a fundamental understanding of the entire angiogenic process and of the role and function of angiogenic inhibitors, in particular, is still lacking. We have developed a two-dimensional mathematical model, which takes into account the complex interactions between endothelial cells, proteolytic enzymes, tumor angiogenic factors and inhibitors. The model serves as a tool in order to investigate different possible functions of the angiogenic inhibitors as well as the mechanisms leading to experimentally observed phenomena during the angiogenic process.