title: Cryptosporidium parvum-induced ileo-caecal adenocarcinoma and Wnt signaling in a mouse model.
abstract: Cryptosporidium species are apicomplexan protozoans that are found worldwide. These parasites constitute a large risk to human and animal health. They cause self-limited diarrhea in immunocompetent hosts and a life-threatening disease in immunocompromised hosts. Interestingly, Cryptosporidium parvum has been related to digestive carcinogenesis in humans. Consistent with a potential tumorigenic role of this parasite, in an original reproducible animal model of chronic cryptosporidiosis based on dexamethasone-treated or untreated adult SCID mice, we formerly reported that C. parvum (strains of animal and human origin) is able to induce digestive adenocarcinoma even in infections induced with very low inoculum. The aim of this study was to further characterize this animal model and to explore metabolic pathways potentially involved in the development of C. parvum-induced ileo-caecal oncogenesis. We searched for alterations in genes or proteins commonly involved in cell cycle, differentiation or cell migration, such as β-catenin, Apc, E-cadherin, Kras and p53. After infection of animals with C. parvum we demonstrated immunohistochemical abnormal localization of Wnt signaling pathway components and p53. Mutations in the selected loci of studied genes were not found after high-throughput sequencing. Furthermore, alterations in the ultrastructure of adherens junctions of the ileo-caecal neoplastic epithelia of C. parvum-infected mice were recorded using transmission electron microscopy. In conclusion, we found for the first time that the Wnt signaling pathway, and particularly the cytoskeleton network, seems to be pivotal for the development of the C. parvum-induced neoplastic process and cell migration of transformed cells. Furthermore, this model is a valuable tool in understanding the host-pathogen interactions associated with the intricate infection process of this parasite, which is able to modulate host cytoskeleton activities and several host-cell biological processes and remains a significant cause of infection worldwide.
authors.affiliation: Ecologie et biodiversité, Faculté Libre des Sciences et Technologies de Lille, Université Catholique de Lille, Université Lille Nord de France, 59020 Lille, France. Biologie et Diversité des Pathogènes Eucaryotes Emergents (BDEEP), Centre d'Infection et d'Immunité de Lille (CIIL), Institut Pasteur de Lille, INSERM U1019, CNRS UMR 8402, Université Lille Nord de France, 59021 Lille, France.
authors.forename: Sadia
authors.initials: S
authors.lastname: Benamrouz
authors.affiliation: Ecologie et biodiversité, Faculté Libre des Sciences et Technologies de Lille, Université Catholique de Lille, Université Lille Nord de France, 59020 Lille, France. Biologie et Diversité des Pathogènes Eucaryotes Emergents (BDEEP), Centre d'Infection et d'Immunité de Lille (CIIL), Institut Pasteur de Lille, INSERM U1019, CNRS UMR 8402, Université Lille Nord de France, 59021 Lille, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Conseil
authors.affiliation: Biologie et Diversité des Pathogènes Eucaryotes Emergents (BDEEP), Centre d'Infection et d'Immunité de Lille (CIIL), Institut Pasteur de Lille, INSERM U1019, CNRS UMR 8402, Université Lille Nord de France, 59021 Lille, France. Faculté de Pharmacie, Université Lille Nord de France, 59021 Lille, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Chabé
authors.affiliation: Academic Department of Pathology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Marleen
authors.initials: M
authors.lastname: Praet
authors.affiliation: PEGASE-Biosciences, Institut Pasteur de Lille, F-59021 Lille, France. Gene Diffusion, 59501 Douai, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Audebert
authors.affiliation: PEGASE-Biosciences, Institut Pasteur de Lille, F-59021 Lille, France. Transcriptomic and Applied Genomic (TAG), Centre d'Infection et d'Immunité de Lille (CIIL), Institut Pasteur de Lille, INSERM U1019, CNRS UMR 8404, Université Lille Nord de France, 59021 Lille, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Blervaque
authors.affiliation: Biologie et Diversité des Pathogènes Eucaryotes Emergents (BDEEP), Centre d'Infection et d'Immunité de Lille (CIIL), Institut Pasteur de Lille, INSERM U1019, CNRS UMR 8402, Université Lille Nord de France, 59021 Lille, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Guyot
authors.affiliation: Biologie et Diversité des Pathogènes Eucaryotes Emergents (BDEEP), Centre d'Infection et d'Immunité de Lille (CIIL), Institut Pasteur de Lille, INSERM U1019, CNRS UMR 8402, Université Lille Nord de France, 59021 Lille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gazzola
authors.affiliation: Plateforme d'Expérimentations et de Hautes Technologies Animales, Institut Pasteur de Lille, 59021 Lille, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Mouray
authors.affiliation: Plateforme d'Expérimentations et de Hautes Technologies Animales, Institut Pasteur de Lille, 59021 Lille, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Chassat
authors.affiliation: Service d'Anatomie et de Cytologie Pathologiques, Groupe Hospitalier de l'Université Catholique de Lille, 59020 Lille, France.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Delaire
authors.affiliation: Centre Hospitalier Régional et Universitaire de Lille, Université Lille Nord de France, 59000 Lille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Goetinck
authors.affiliation: Biologie et Diversité des Pathogènes Eucaryotes Emergents (BDEEP), Centre d'Infection et d'Immunité de Lille (CIIL), Institut Pasteur de Lille, INSERM U1019, CNRS UMR 8402, Université Lille Nord de France, 59021 Lille, France.
authors.forename: Nausicaa
authors.initials: N
authors.lastname: Gantois
authors.affiliation: Biologie et Diversité des Pathogènes Eucaryotes Emergents (BDEEP), Centre d'Infection et d'Immunité de Lille (CIIL), Institut Pasteur de Lille, INSERM U1019, CNRS UMR 8402, Université Lille Nord de France, 59021 Lille, France. Centre AZM pour la Recherche en Biotechnologie et ses Applications, Laboratoire Microbiologie, Santé et Environnement, Université Libanaise, Tripoli, Lebanon.
authors.forename: Marwan
authors.initials: M
authors.lastname: Osman
authors.affiliation: Inserm U1003, Laboratoire de Physiologie Cellulaire, Université Lille 1, 59655 Villeneuve d'Ascq CEDEX, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Slomianny
authors.affiliation: Unité de Glycobiologie Structurale et Fonctionnelle, UMR CNRS 8576, IFR 147, Université Lille1, 59650 Villeneuve d'Ascq, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Dehennaut
authors.affiliation: Unité de Glycobiologie Structurale et Fonctionnelle, UMR CNRS 8576, IFR 147, Université Lille1, 59650 Villeneuve d'Ascq, France.
authors.forename: Tony
authors.initials: T
authors.lastname: Lefebvre
authors.affiliation: Biologie et Diversité des Pathogènes Eucaryotes Emergents (BDEEP), Centre d'Infection et d'Immunité de Lille (CIIL), Institut Pasteur de Lille, INSERM U1019, CNRS UMR 8402, Université Lille Nord de France, 59021 Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Viscogliosi
authors.affiliation: Academic Department of Pathology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Claude
authors.initials: C
authors.lastname: Cuvelier
authors.affiliation: Biologie et Diversité des Pathogènes Eucaryotes Emergents (BDEEP), Centre d'Infection et d'Immunité de Lille (CIIL), Institut Pasteur de Lille, INSERM U1019, CNRS UMR 8402, Université Lille Nord de France, 59021 Lille, France. Centre Hospitalier Régional et Universitaire de Lille, Université Lille Nord de France, 59000 Lille, France.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Dei-Cas
authors.affiliation: Service d'Anatomie et de Cytologie Pathologiques, Groupe Hospitalier de l'Université Catholique de Lille, 59020 Lille, France.
authors.forename: Colette
authors.initials: C
authors.lastname: Creusy
authors.affiliation: Biologie et Diversité des Pathogènes Eucaryotes Emergents (BDEEP), Centre d'Infection et d'Immunité de Lille (CIIL), Institut Pasteur de Lille, INSERM U1019, CNRS UMR 8402, Université Lille Nord de France, 59021 Lille, France. gabriela.certad@pasteur-lille.fr.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Certad
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000469:parasitology*; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D016785:Cryptosporidium parvum / Q000502:physiology*; D004195:Disease Models, Animal; D016158:Genes, p53; D011905:Genes, ras; D007414:Intestinal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000469:parasitology*; D051379:Mice; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D051153:Wnt Proteins; D051176:beta Catenin
keywords: Cryptosporidiosis; Cytoskeleton; Digestive cancer; SCID mouse model; Wnt pathway