Modeling and Simulation of EGF-CSF-1 pathway to Investigate Glioma - Macrophage Interaction in Brain Tumors

Glioblastoma multiform (GBM) is one of the most lethal forms of brain cancers. The biggest difficulties for diagnostics and treatment of GBM underlie in its dynamic and complex macro and microenvironment. Glioma cells, stromal cells and tumor-associated immune cells (microglia/macrophage-TAMs) become a complex tissue with their physical and chemical communication network. TAMs are the predominant infiltrating immune cells in malignant GBMs and stimulate tumor invasion, angiogenesis, and metastasis. The epidermal growth factor (EGF) and colony stimulating factor 1 (CSF-1) paracrine signaling loop plays a key role in communication between glioma cells and TAMs. We developed a mathematical model to investigate macrophage-glioma cell interactions using CSF-1 and EGF paracrine-acting agents. Our model presents change of EGF and CSF-1 concentration both on the surfaces of cells and within a well-defined tumor microenvironment, in a domain, with respect to interaction time and distance between TAMs and glioma cells. Our simulation results confirm that from low-grade glioma to high-grade glioma, concentration of CSF-1 increases both on the surfaces of macrophages and within the domain. Therefore, reproduction and adsorption of CSF-1 correlates with the grade of malignancy in human gliomas, which is a good agreement with recent findings