title: Dynamic tumor growth patterns in a novel murine model of colorectal cancer.
abstract: Colorectal cancer often arises from adenomatous colonic polyps. Polyps can grow and progress to cancer, but may also remain static in size, regress, or resolve. Predicting which polyps progress and which remain benign is difficult. We developed a novel long-lived murine model of colorectal cancer with tumors that can be followed by colonoscopy. Our aim was to assess whether these tumors have similar growth patterns and histologic fates to human colorectal polyps to identify features to aid in risk stratification of colonic tumors. Long-lived Apc(Min/+) mice were treated with dextran sodium sulfate to promote colonic tumorigenesis. Tumor growth patterns were characterized by serial colonoscopy with biopsies obtained for immunohistochemistry and gene expression profiling. Tumors grew, remained static, regressed, or resolved over time with different relative frequencies. Newly developed tumors demonstrated higher rates of growth and resolution than more established tumors that tended to remain static in size. Colonic tumors were hyperplastic lesions (3%), adenomas (73%), intramucosal carcinomas (20%), or adenocarcinomas (3%). Interestingly, the level of β-catenin was higher in adenomas that became intratumoral carcinomas than those that failed to progress. In addition, differentially expressed genes between adenomas and intramucosal carcinomas were identified. This novel murine model of intestinal tumorigenesis develops colonic tumors that can be monitored by serial colonoscopy, mirror growth patterns seen in human colorectal polyps, and progress to colorectal cancer. Further characterization of cellular and molecular features is needed to determine which features can be used to risk-stratify polyps for progression to colorectal cancer and potentially guide prevention strategies.
authors.affiliation: University of Wisconsin-Madison K4/532 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792. rbhalberg@medicine.wisc.edu.
authors.forename: Terrah J
authors.initials: TJ
authors.lastname: Paul Olson
authors.forename: Jamie N
authors.initials: JN
authors.lastname: Hadac
authors.forename: Chelsie K
authors.initials: CK
authors.lastname: Sievers
authors.forename: Alyssa A
authors.initials: AA
authors.lastname: Leystra
authors.forename: Dustin A
authors.initials: DA
authors.lastname: Deming
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Zahm
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Albrecht
authors.forename: Alice
authors.initials: A
authors.lastname: Nomura
authors.forename: Laura A
authors.initials: LA
authors.lastname: Nettekoven
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Plesh
authors.forename: Linda
authors.initials: L
authors.lastname: Clipson
authors.forename: Ruth
authors.initials: R
authors.lastname: Sullivan
authors.forename: Michael A
authors.initials: MA
authors.lastname: Newton
authors.forename: William R
authors.initials: WR
authors.lastname: Schelman
authors.forename: Richard B
authors.initials: RB
authors.lastname: Halberg
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D018256:Adenomatous Polyps / Q000473:pathology; D000818:Animals; D003111:Colonic Polyps / Q000473:pathology*; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D013997:Time Factors
chemical_list: D025601:Adenomatous Polyposis Coli Protein