Abstract B29: Snail regulates extracellular matrix-mediated VEGFR3 expression in developmental and tumor angiogenesis

Abstract

Abstract Snail family is a zinc finger transcription factor and involved in epithelial branching morphogenesis and EMT by altering the ability of polarity, motility, and adhesion. The expression of Snail family in developing and tumor vessels has been suggested, however, the precise expression pattern and cellular function of Snail remain to be unclear. We identified Snail as an angiogenic regulator through inducing VEGFR3 under extracellular matrix (ECM)-meditated signalings. Snail was upregulated in the postnatally developing retinal endothelial cells (ECs) and in the vessels lining ductal breast tumors. In vitro endothelial sprouting assay indicated that knockdown or ectopic expression of Snail impaired EC sprouting on ECM. Moreover, Snail colocalized with VEGFR3 and upregulated VEGFR3 mRNA by cooperating with early growth response protein-1 in ECs. In the developing vessel model, intraperitoneal injection with stable Snail siRNA in postnatal mice demonstrated that Snail loss attenuated the formation of the vascular plexus not only by impairing vertical sprouting vessels but also by downregulating VEGFR3. Furthermore, in MMTV-PyMT breast tumors, Snail was strongly expressed in endothelial vessels around ductal breast tumors along with VEGFR3 expression. These data demonstrate that Snail contributes to vascular morphogenesis by upregulating VEGFR3. ECM-Snail-VEGFR3 axis may play crucial roles in disorganized vascular network in solid tumors. Citation Format: Jeong Ae Park, Ho-Young Lee, Young-Guen Kwon. Snail regulates extracellular matrix-mediated VEGFR3 expression in developmental and tumor angiogenesis. [abstract]. In: Proceedings of the AACR Special Conference: Developmental Biology and Cancer; Nov 30-Dec 3, 2015; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(4_Suppl):Abstract nr B29.