A Biosensor Mouse To Predict The Dissociation And Spread Of Pancreatic Cancer

E-cadherin-mediated cell-cell junctions play a physical role in maintaining normal epithelial architecture. The disruption or deregulation of these adhesions in cancer can lead to the collapse of tumor epithelia that precedes invasion and subsequent metastasis. Here, we have generated an E-cadherin-GFP(FRAP) biosensor mouse, which enables intravital photobleaching and quantification of E-cadherin mobility in live tissue, without affecting normal biology. We demonstrate using FRAP or FLIP, the broad applications of this mouse to examine E-cadherin regulation in multiple tissues including mammary, brain, liver and kidney, while specifically monitoring E-cadherin mobility during disease progression in the pancreas. We assess E-cadherin stability in native pancreatic tissue, upon genetic manipulation involving Kras and p53 or in response to anti-invasive drug treatment, and reveal new insights into the dynamic remodeling of E-cadherin during in situ cancer progression. Photobleaching in the E-cadherin-GFP(FRAP) mouse correlate directly with epithelial integrity and mechanical strength making the biosensor mouse a valuable tool to fundamentally expand our understanding of E-cadherin-mediated events in native micro-environments. This abstract is also being presented as Poster B23. Citation Format: David Herrmann, Zahra Erami, Sean Warren, Max Nobis, Astrid Magenau, Morghan Lucas, Claire Vennin, Ewan J. McGhee, Wilfred Leung, Nadine Reischmann, Agata Mrowinska, Juliane P. Schwarz, Shereen Kadir, Saadia A. Karim, Andrew D. Campbell, David Gallego-Ortega, Jeffry Evans, Owen J. Sansom, Jennifer P. Morton, Kurt I. Anderson, Paul Timpson. A biosensor mouse to predict the dissociation and spread of pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr PR07.