Abstract 3391: SCUBE2 is a co-receptor for VEGFR2 in tumor angiogenesis

Abstract

Abstract Signal peptide-complement protein C1r/C1s, Uegf, and Bmp1 (CUB)-epidermal growth factor (EGF) domain-containing protein 2 (SCUBE2) is a peripheral membrane protein expressed in normal tissue and tumor vascular endothelial cells (ECs); however, its role in angiogenesis remains poorly understood. In this study, we show that endothelial SCUBE2 is upregulated by hypoxia and acts as a co-receptor for VEGFR2 to facilitate VEGF binding to VEGFR2 and augment its signals including VEGFR2 phosphorylation and p44/42 MAPKs/Akt activation, thus promotes cell proliferation and tubule formation in ECs. While physiological angiogenesis remained normal in the endothelial ablation of Scube2 in mice, pathological angiogenesis in experimental tumors was altered, resulting in smaller tumors and reduced microvascular density. To simulate the angiogenic environment of the tumor, Scube2-deficient ECs were isolated and propagated in vitro with VEGF. Mutant ECs exhibited marked reduction in binding of VEGF, proliferation and sprouting responses to VEGF as well as downstream signal activation. Our results reveal that SCUBE2 might act as a novel co-receptor for VEGFR2, and point that targeting such SCUBE2 function in human ECs may represent a potential anti-tumor strategy by inhibiting tumor angiogenesis. Citation Format: Yuh-Charn Lin, Ruey-Bing Yang. SCUBE2 is a co-receptor for VEGFR2 in tumor angiogenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3391.