Background: Colorectal-cancer (CRC) research has greatly benefited from the availability of small animal tumor models.\r\nSpontaneous and chemically-induced CRC models are widely used yet limited in their resemblance to human disease and\r\nare often prolonged, not accurately repetitive, and associated with inflammatory side effects. In-situ murine or human\r\ntumor implantation in the gastrointestinal tract of mice is extremely challenging, and limited by inter-animal variability and\r\nprocedure-related complications and mortality. As a result, in frequent studies CRC is implanted in distal sites, most\r\ncommonly the subcutaneous region, an approach that is greatly limited by the absence of normal gastrointestinal tumor\r\nmilieu and has substantial effects on tumor development.\r\nAims: In this study we aimed to develop a well-tolerated repetitive tool to study CRC in small animals by adapting the\r\nmurine colonoscopy system to serve as a platform for colonic sub-mucosal orthotopic implantation of human and murine\r\nCRC tumor cells.\r\nResults: We report the establishment of a novel small-animal CRC model that is minimally invasive, rapid, well-tolerated,\r\nhighly reproducible, and confers precise control of tumor number, location and growth rate. Moreover, we show that this\r\nmodel uniquely allows the side-by-side induction of distinct genetically manipulated tumors, enabling the mechanistic\r\nstudy of tumor interaction and cross-talk within the native intestinal microenvironment.\r\nConclusions: Employment of this new approach may represent a major technical advance for the in-vivo study of CRC.
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