In Vitro and in Vivo Analyses of the Effects of Sunitinib on Endothelial Cell‐Surface Vascular Endothelial Growth Factor Receptor‐2

Abstract

Angiogenesis, the recruitment of new vasculature, is a critical step for cancer development. Vascular endothelial growth factor A (VEGFA) is a major factor in the recruitment of blood vessels in which it binds to vascular endothelial growth factor receptor-2 (VEGFR2), among others, to promote endothelial cell migration and proliferation. Sunitinib, an anti-angiogenic tyrosine kinase inhibitor drug, is an inhibitor of VEGFR2 signaling and has been approved for use in gastrointestinal and renal cell carcinoma by the US Food and Drug Administration. Quantitative flow cytometry was used to understand the effects of sunitinib on the number of endothelial cell-surface VEGFR2 in vitro and in vivo. We find that sunitinib treatment increases the number of functional VEGFR2 on the cell surface of endothelial cells in vitro. We used a breast cancer xenograft mouse model to determine the effects of administration of sunitinib in vivo and found by contrast the numbers of cell-surface VEGFR2 on endothelial cells were decreased. This data illustrates the complexity of drug effects in vitro and in vivo and suggests a better understanding is needed.