Winnie-APCMin/+ Mice: A Spontaneous Model of Colitis-Associated Colorectal Cancer Combining Genetics and Inflammation

• Published in: International journal of molecular sciences Vol. 21; no. 8; p. 2972
• Main Authors: De Santis, Stefania, Verna, Giulio, Serino, Grazia, Armentano, Raffaele, Cavalcanti, Elisabetta, Liso, Marina, Dicarlo, Manuela, Coletta, Sergio, Mastronardi, Mauro, Lippolis, Antonio, Tafaro, Angela, Santino, Angelo, Pinto, Aldo, Campiglia, Pietro, Huang, Alex Y., Cominelli, Fabio, Pizarro, Theresa T., Chieppa, Marcello
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 23.04.2020; MDPI
• Subjects: Aberrant Crypt Foci; Animal models; Apoptosis; Cancer; Colitis; Colon; Colorectal cancer; Colorectal carcinoma; Gene expression; Genetic disorders; Inflammation; Inflammatory bowel disease; Intestine; Lesions; Mucin; murine model; Mutation; Pathogenesis; Polyposis; Polyps; Risk analysis; Risk factors; Rodents
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21082972

(1) Background: Colorectal cancer (CRC) is among the best examples of the relationship between inflammation and increased cancer risk. (2) Methods: To examine the effects of spontaneous low-grade chronic inflammation on the pathogenesis of CRC, we developed a new murine model of colitis-associated cancer (CAC) by crossing Mucin 2 mutated mice (Winnie) with ApcMin/+ mice. (3) Results: The resulting Winnie-ApcMin/+ model combines an inflammatory background with a genetic predisposition to small intestinal polyposis. Winnie-ApcMin/+ mice show an early occurrence of inflammatory signs and dysplastic lesions in the distal colon with a specific molecular signature. (4) Conclusion: The Winnie-ApcMin/+ model is a perfect model to demonstrate that chronic inflammation represents a crucial risk factor for the onset and progression of tumoral lesions in individuals genetically predisposed to CRC.