Snail and E47 repressors ofE-cadherininduce distinct invasive and angiogenic properties in vivo

Abstract

The transcription factors Snail and E47 are direct repressors of E-cadherin, with both inducing a full epithelial-mesenchymal transition and invasive behaviour in vitro when expressed in the prototypic epithelial MDCK cell line. The role of these repressors in the invasive process and in other tumorigenic properties is, nevertheless, still poorly understood. However, organotypic cultures and in vivo transplantation assays indicate that cells expressing MDCK-Snail and MDCK-E47 exhibit significant differences. MDCK-Snail cells have a higher infiltrative potential than MDCK-E47 cells. Interestingly, both cell types induce angiogenesis of the host stromal tissue in transplantation assays, but this property is greatly enhanced in transplants of MDCK-E47 cells. Xenografted tumours induced in nude mice also show signs of strong angiogenic potential, again markedly increased in tumours induced by MDCK-E47 which exhibit a higher vessel density and proliferation rate than those induced by MDCK-Snail cells. These results suggest differential roles for Snail and E47 E-cadherin repressors in tumour progression where Snail is implicated in promoting the initial invasion and E47 plays an active role in tumour cell growth by promoting angiogenesis.