Abstract 4329: In vivo visualization of epithelial-mesenchymal transition in real time using a rapidly tuneable E-cadherin

Abstract

Abstract The transformation of benign tumour cells to invasive, metastatic tumour cells involves the dynamic redeployment of factors involved in cell adhesion and motility collectively known as epithelial-mesenchymal transition (EMT). While the loss of E-cadherin localization at cell-cell junctions is a hallmark feature of EMT, the impact of E-cadherin re-expression and modulation in metastatic cancer cells at distinct steps of the metastatic cascade has not been explored. To address this, we developed an intravital imaging approach that allows us to visualize changes in behaviour of highly metastatic MDA-MB-231-LN breast cancer cells in real time using a dynamically tuneable form of E-cadherin. Here, we show that upon induction of E-cadherin in vivo, cell-cell adherens junctions begin to appear within 30 minutes, concurrent with the accumulation of plasma membrane-localized E-cadherin and the retraction of tumour cell protrusions and the induction of a rounded epithelial-like morphology. Furthermore, subsequent depletion of E-cadherin results in a rapid reversion to the mesenchymal morphology. These studies demonstrate that E-cadherin is sufficient to induce a rapid mesenchymal to epithelial transition in vivo, and that sustained E-cadherin expression is required to maintain this less invasive morphology. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4329.