title: High Endogenous Expression of Chitinase 3-Like 1 and Excessive Epithelial Proliferation with Colonic Tumor Formation in MOLF/EiJ Mice.
abstract: Colorectal cancer (CRC) development is mediated by uncontrolled survival and proliferation of tumor progenitor cells. Using animal models to identify and study host-derived factors that underlie this process can aid interventions in preventing tumor expansion and metastasis. In healthy steady states in humans and mice (e.g. C57BL/6 strain), colonic Chitinase 3-like 1 (CHI3L1) gene expression is undetectable. However, this expression can be induced during intestinal inflammation and tumorigenesis where CHI3L1 plays an important role in tissue restitution and cell proliferation. Here, we show that a wild-derived mouse strain MOLF/EiJ expresses high levels of colonic epithelial CHI3L1 at the steady state due to several nucleotide polymorphisms in the proximal promoter regions of the CHI3L1 gene. Interestingly, these mice spontaneously developed polypoid nodules in the colon with signs of immune cell infiltrations at steady state. The CHI3L1 positive colonic epithelial cells were highly proliferative and exhibited malignant transformation and expansion when exposed in vivo to azoxymethane, one of the well-known colonic carcinogens.
authors.affiliation: Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America.
authors.forename: Daren
authors.initials: D
authors.lastname: Low
authors.affiliation: Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America.
authors.forename: Arianna K
authors.initials: AK
authors.lastname: DeGruttola
authors.affiliation: Department of Molecular Biology, Petrozavodsk State University, 185910, Petrozavodsk, Republic of Karelia, Russia; Graduate Program in Genetics, Sackler School of Biomedical Sciences, Tufts University, Boston, MA, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Poltrak
authors.affiliation: Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizoguchi
authors.affiliation: Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America.
authors.forename: Mari
authors.initials: M
authors.lastname: Mino-Kenudson
authors.affiliation: Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America; Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America.
authors.forename: Emiko
authors.initials: E
authors.lastname: Mizoguchi
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D000071451:Chitinase-3-Like Protein 1; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal
chemical_list: C509289:Chil1 protein, mouse; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins