Cryptosporidium parvum-induced ileo-caecal adenocarcinoma and WNT signaling in a rodent model

DMM Disease Models and Mechanisms
Sadia Benamrouz-Vanneste1, Valérie Conseil1, Magali Chabé2, Marleen Praet3, Christophe Audebert4, Renaud Blervaque5, Karine Guyot2, Sophie Gazzola2, Anthony Mouray6, Thierry Chassat6, Baptiste Delaire7, Nathalie Goetinck8, Nausicaa Gantois2, Marwan Osman9, Natalia Prevarskaya10, Vanessa Dehennaut11, Tony Lefebvre11, Éric Viscogliosi2, Claude Cuvelier3, Sergio L. Vargas8, Colette Creusy7, Gabriela Certad2
1Ecologie & Biodiversité, Université Catholique de Lille, Lille, France;
2BDEEP, CIIL, Institut Pasteur de Lille, Lille, France;
3UGENT - Universiteit Gent = Ghent University (St. Pietersnieuwstraat 33, 9000 Gent, - Belgique)
4Institut Pasteur de Lille (1 Rue du Professeur Calmette - Lille Cedex - 59019 - France)
5Transcriptomic and Applied Genomic (TAG), CIIL, IPL, Lille, France;
6Plateforme d'Experimentations et de Hautes Technologies Animales, Inst. Pasteur de Lille, France;
7Service d'Anatomie et de Cytologie Pathologiques, Lille, France;
8Centre Hospitalier Regional et Universitaire de Lille, Universit&eacute Lille Nord de France, France;
9Laboratoire Microbiologie, Santé et Environnement, Universite Libanaise, Tripoli, Lebanon;
10Laboratoire de Physiologie Cellulaire, Université Lille1, Villeneuve d'Ascq, Lille, France;
11Unité de Glycobiologie Structurale et Fonctionnelle, Université Lille1, Lille, France

Tóm tắt

Abstract Cryptosporidium species are worldwide spread apicomplexan protozoan. These parasites constitute a significant risk to humans and animals. 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. Consistently 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 C. parvum-induced neoplastic process and cell migration of transformed cells. Furthermore, this model is a valuable tool to contribute to the comprehension of the host-pathogen interactions associated to the intricate infection process due to this parasite, which is able to modulate host cytoskeleton activities and several host-cell biological processes and that remains a significant cause of infection worldwide.

Từ khóa


Tài liệu tham khảo

Aliouat, 1995, Pneumocystitis carinii organisms from in vitro culture are highly infectious to the nude rat, Parasitol. Res., 81, 82, 10.1007/BF00932421

Benamrouz, 2012, Cryptosporidium parvum infection in SCID mice infected with only one oocyst: qPCR assessment of parasite replication in tissues and development of digestive cancer, Plos One, 7, e51232, 10.1371/journal.pone.0051232

Buda, 2004, Cytoskeletal network in colon cancer: from genes to clinical application, Int. J. Biochem. Cell Biol., 36, 759, 10.1016/j.biocel.2003.09.004

Bulckaen, 2008, Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging, Am. J. Physiol., 294, H1562

Certad, 2007, Cryptosporidium parvum, a potential cause of colic adenocarcinoma, Infect. Agent. Cancer, 2, 22, 10.1186/1750-9378-2-22

Certad, 2010, Fulminant cryptosporidiosis associated with digestive adenocarcinoma in SCID mice infected with Cryptosporidium parvum TUM1 strain, Int. J. Parasitol., 40, 1469, 10.1016/j.ijpara.2010.07.007

Certad, 2010, Development of Cryptosporidium parvum induced gastro-intestinal neoplasia in SCID mice: Severity of lesions is correlated with infection intensity, Am. J. Trop. Med. Hyg., 82, 257, 10.4269/ajtmh.2010.09-0309

Certad, 2012, Fulminant cryptosporidiosis after near-drowning: a human Cryptosporidium parvum strain implicated in invasive gastrointestinal adenocarcinoma and cholangiocarcinoma in an experimental model, Appl. Environ. Microbiol., 78, 1746, 10.1128/AEM.06457-11

Chalmers, 2013, Looking for Cryptosporidium: the application of advances in detection and diagnosis, Trends Parasitol., 29, 237, 10.1016/j.pt.2013.03.001

Cooper, 2000, Dysplasia and cancer in the dextran sulfate sodium mouse colitis model. Relevance to colitis-associated neoplasia in the human: a study of histopathology, B-catenin and p53 expression and the role of inflammation, Carcinogenesis, 21, 757, 10.1093/carcin/21.4.757

Cossart, 2004, Bacterial invasion: the paradigms of enteroinvasive pathogens, Science, 304, 242, 10.1126/science.1090124

Deng, 2004, Cryptosporidium parvum regulation of human epithelial cell gene expression, Int. J. Parasitol., 34, 73, 10.1016/j.ijpara.2003.10.001

Everly, 2004, Accumulation of cytoplasmic beta-catenin and nuclear glycogen synthase kinase 3beta in Epstein-Barr virus-infected cells, J. Virol., 78, 11648, 10.1128/JVI.78.21.11648-11655.2004

Giles, 2003, Caught up in a Wnt storm: Wnt signaling in cancer, Biochim. Biophys. Acta, 1653, 1

Haller, 2010, Cytoplasmic sequestration of p53 promotes survival in leukocytes transformed by Theileria, Oncogene, 29, 3079, 10.1038/onc.2010.61

Hu, 2009, Detection of K-ras mutations in azoxymethane-induced aberrant crypt foci in mice using LNA-mediated real-time PCR clamping and mutant-specific probes, Mutat. Res., 677, 27, 10.1016/j.mrgentox.2009.05.003

Hughes, 2002, Adenomatous polyposis coli truncation alters cytoskeletal structure and microtubule stability in early intestinal tumorigenesis, J. Gastrointest. Surg., 6, 868, 10.1016/S1091-255X(02)00065-3

Janssen, 2006, APC and oncogenic KRAS are synergistic in enhancing Wnt signaling in intestinal tumor formation and progression, Gastroenterology, 131, 1096, 10.1053/j.gastro.2006.08.011

Johnson, 2009, Regulation of beta-catenin trafficking to the membrane in living cells, Cell. Signal., 21, 339, 10.1016/j.cellsig.2008.11.004

Kuraguchi, 2000, Tumor-associated Apc mutations in Mlh1−/− Apc1638N mice reveal a mutational signature of Mlh1 deficiency, Oncogene, 19, 5755, 10.1038/sj.onc.1203962

Lambert, 2011, Aberrant DNA methylation distinguishes hepatocellular carcinoma associated with HBV and HCV infection and alcohol intake, J. Hepatol., 54, 705, 10.1016/j.jhep.2010.07.027

Lechel, 2008, Rho GTPase and Wnt signaling pathways in hepatocarcinogenesis, Gastroenterology, 134, 875, 10.1053/j.gastro.2008.01.055

Liu, 2009, Biphasic modulation of apoptotic pathways in Cryptosporidium parvum-infected human intestinal epithelial cells, Infect. Immun., 77, 837, 10.1128/IAI.00955-08

O’Brate, 2003, The importance of p53 location: nuclear or cytoplasmic zip code?, Drug Resist. Updat., 6, 313, 10.1016/j.drup.2003.10.004

O’Hara, 2011, The cell biology of cryptosporidium infection, Microbes Infect., 13, 721, 10.1016/j.micinf.2011.03.008

Odenwald, 2013, APC/β-catenin-rich complexes at membrane protrusions regulate mammary tumor cell migration and mesenchymal morphology, BMC Cancer, 13, 12, 10.1186/1471-2407-13-12

Okhuysen, 1999, Virulence of three distinct Cryptosporidium parvum isolates for healthy adults, J. Infect. Dis., 180, 1275, 10.1086/315033

Olivier-Van Stichelen, 2012, Serum-stimulated cell cycle entry promotes ncOGT synthesis required for cyclin D expression, Oncogenesis, 1, e36, 10.1038/oncsis.2012.36

Palluault, 1992, High osmotic pressure for Pneumocystis carinii London Resin White embedding enables fine immunocytochemistry studies: I. Golgi complex and cell-wall synthesis, Parasitol. Res., 78, 482, 10.1007/BF00931568

Patel, 2008, Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992–2003, Ann. Intern. Med., 148, 728, 10.7326/0003-4819-148-10-200805200-00005

Ramirez, 2004, A review of the biology and epidemiology of cryptosporidiosis in humans and animals, Microbes Infect., 6, 773, 10.1016/j.micinf.2004.02.021

Rowan, 2011, Defining established and emerging microbial risks in the aquatic environment: current knowledge, implications, and outlooks, Int. J. Microbiol., 2011, 462832, 10.1155/2011/462832

Segditsas, 2006, Colorectal cancer and genetic alterations in the Wnt pathway, Oncogene, 25, 7531, 10.1038/sj.onc.1210059

Shebl, 2012, Opportunistic intestinal infections and risk of colorectal cancer among people with AIDS, AIDS Res. Hum. Retroviruses, 28, 994, 10.1089/aid.2011.0185

Sulżyc-Bielicka, 2007, Cryptosporidiosis in patients with colorectal cancer, J. Parasitol., 93, 722, 10.1645/GE-1025R1.1

Sulżyc-Bielicka, 2012, Prevalence of Cryptosporidium sp. in patients with colorectal cancer, Pol. Przegl. Chir., 84, 348, 10.2478/v10035-012-0058-4

Takahashi, 2004, Gene mutations and altered gene expression in azoxymethane-induced colon carcinogenesis in rodents, Cancer Sci., 95, 475, 10.1111/j.1349-7006.2004.tb03235.x

Takahashi, 2000, Altered expression of beta-catenin, inducible nitric oxide synthase and cyclooxygenase-2 in azoxymethane-induced rat colon carcinogenesis, Carcinogenesis, 21, 1319, 10.1093/carcin/21.7.1319

Tomizawa, 2004, Allogeneic hematopoietic stem cell transplantation for seven children with X-linked hyper-IgM syndrome: a single center experience, Am. J. Hematol., 76, 33, 10.1002/ajh.20044

Yoder, 2010, Cryptosporidium surveillance and risk factors in the United States, Exp. Parasitol., 124, 31, 10.1016/j.exppara.2009.09.020

Thông tin
Thông tin xuất bản

DMM Disease Models and Mechanisms

Thông tin tác giả