utilization of murine colonoscopy for orthotopic implantation of colorectal cancer利用小鼠原位移植的结肠镜检查结肠直肠癌.pdfVIP

Utilization of Murine Colonoscopy for Orthotopic Implantation of Colorectal Cancer 1,2 1 1 1 2 1 Ehud Zigmond *, Zamir Halpern , Eran Elinav , Eli Brazowski , Steffen Jung , Chen Varol * 1The Research Center for Digestive Tract and Liver Diseases, Sourasky Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel, 2 Department of Immunology, Weizmann Institute of Science, Rehovot, Israel Abstract Background: Colorectal-cancer (CRC) research has greatly benefited from the availability of small animal tumor models. Spontaneous and chemically-induced CRC models are widely used yet limited in their resemblance to human disease and are often prolonged, not accurately repetitive, and associated with inflammatory side effects. In-situ murine or human tumor implantation in the gastrointestinal tract of mice is extremely challenging, and limited by inter-animal variability and procedure-related complications and mortality. As a result, in frequent studies CRC is implanted in distal sites, most commonly the subcutaneous region, an approach that is greatly limited by the absence of normal gastrointestinal tumor milieu and has substantial effects on tumor development. Aims: In this study we aimed to develop a well-tolerated repetitive tool to study CRC in small animals by adapting the murine colonoscopy system to serve as a platform for colonic sub-mucosal orthotopic implantation of human and murine CRC tumor cells. Results: We report the establishment of a novel small-animal CRC model that is minimally invasive, rapid, well-tolerated, highly reproducible, and confers precise control of tumor number, location and growth rate. Moreover, we show that this