UC Irvine

Objective

In glioblastoma, the crosstalk between vascular endothelial cells (VECs) and glioma stem cells (GSCs) has been shown to enhance tumor growth. We propose a multiscale mathematical model to study this mechanism, explore tumor growth under various initial and microenvironmental conditions, and investigate the effects of blocking this crosstalk.

Methods

We develop a hybrid continuum-discrete model of highly organized vascularized tumors. VEC-GSC crosstalk is modeled via vascular endothelial growth factor (VEGF) production by tumor cells and by secretion of soluble factors by VECs that promote GSC self-renewal and proliferation.

Results

VEC-GSC crosstalk increases both tumor size and GSC fraction by enhancing GSC activity and neovascular development. VEGF promotes vessel formation, and larger VEGF sources typically increase vessel numbers, which enhances tumor growth and stabilizes the tumor shape. Increasing the initial GSC fraction has a similar effect. Partially disrupting the crosstalk by blocking VEC secretion of GSC promoters reduces tumor size but does not increase invasiveness, which is in contrast to antiangiogenic therapies, which reduce tumor size but may significantly increase tumor invasiveness.

Significance

Multiscale modeling supports the targeting of VEC-GSC crosstalk as a promising approach for cancer therapy.