title: Cholera-toxin suppresses carcinogenesis in a mouse model of inflammation-driven sporadic colon cancer.
abstract: Human studies and clues from animal models have provided important links between gastrointestinal (GI) tract bacteria and colon cancer. Gut microbiota antigenic stimuli play an important role in shaping the intestinal immune responses. Therefore, especially in the case of inflammation-associated colon cancer, gut bacteria antigens may affect tumorigenesis. The present study aimed to investigate the effects of the oral administration of a bacterial product with known immunomodulatory properties on inflammation-driven colorectal neoplasmatogenesis. For that, we used cholera-toxin and a well-established mouse model of colon cancer in which neoplasia is initiated by a single dose of the genotoxic agent azoxymethane (AOM) and subsequently promoted by inflammation caused by the colitogenic substance dextran sodium sulfate (DSS). We found that a single, low, non-pathogenic dose of CT, given orally at the beginning of each DSS treatment cycle downregulated neutrophils and upregulated regulatory T-cells and IL-10 in the colonic mucosa. The CT-induced disruption of the tumor-promoting character of DSS-induced inflammation led to the reduction of the AOM-initiated colonic polypoidogenesis. This result adds value to the emerging notion that certain GI tract bacteria or their products affect the immune system and render the microenvironment of preneoplastic lesions less favorable for promoting their evolution to cancer.
authors.affiliation: Laboratory of Pathology, Laboratory of Biochemistry and Toxicology and Laboratory of Anatomy, Histology and Embryology, Faculty of Health Sciences, School of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece, Department of Agricultural Development, Democritus University of Thrace, Orestiada 68200, Greece and Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Doulberis
authors.affiliation: Laboratory of Biochemistry and Toxicology and.
authors.forename: Katerina
authors.initials: K
authors.lastname: Angelopoulou
authors.affiliation: Laboratory of Pathology, Laboratory of Biochemistry and Toxicology and Laboratory of Anatomy, Histology and Embryology, Faculty of Health Sciences, School of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece, Department of Agricultural Development, Democritus University of Thrace, Orestiada 68200, Greece and Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Eleni
authors.initials: E
authors.lastname: Kaldrymidou
authors.affiliation: Laboratory of Anatomy, Histology and Embryology, Faculty of Health Sciences, School of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Tsingotjidou
authors.affiliation: Department of Agricultural Development, Democritus University of Thrace, Orestiada 68200, Greece and.
authors.forename: Zaphiris
authors.initials: Z
authors.lastname: Abas
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Suzan E
authors.initials: SE
authors.lastname: Erdman
authors.affiliation: Laboratory of Pathology, Laboratory of Biochemistry and Toxicology and Laboratory of Anatomy, Histology and Embryology, Faculty of Health Sciences, School of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece, Department of Agricultural Development, Democritus University of Thrace, Orestiada 68200, Greece and Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA teoput@vet.auth.gr.
authors.forename: Theofilos
authors.initials: T
authors.lastname: Poutahidis
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D063646:Carcinogenesis / Q000187:drug effects*; D002772:Cholera Toxin / Q000494:pharmacology*; D003092:Colitis / Q000139:chemically induced; D003106:Colon / Q000382:microbiology / Q000473:pathology; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D007155:Immunologic Factors / Q000494:pharmacology; D007249:Inflammation / Q000473:pathology; D016753:Interleukin-10 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000517:prevention & control*; D009504:Neutrophils / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D016588:Anticarcinogenic Agents; C556062:IL10 protein, mouse; D007155:Immunologic Factors; D016753:Interleukin-10; D002772:Cholera Toxin