Disease Models & Mechanisms (Jun 2014)

Cryptosporidium parvum-induced ileo-caecal adenocarcinoma and Wnt signaling in a mouse model

  • Sadia Benamrouz,
  • Valerie Conseil,
  • Magali Chabé,
  • Marleen Praet,
  • Christophe Audebert,
  • Renaud Blervaque,
  • Karine Guyot,
  • Sophie Gazzola,
  • Anthony Mouray,
  • Thierry Chassat,
  • Baptiste Delaire,
  • Nathalie Goetinck,
  • Nausicaa Gantois,
  • Marwan Osman,
  • Christian Slomianny,
  • Vanessa Dehennaut,
  • Tony Lefebvre,
  • Eric Viscogliosi,
  • Claude Cuvelier,
  • Eduardo Dei-Cas,
  • Colette Creusy,
  • Gabriela Certad

DOI
https://doi.org/10.1242/dmm.013292
Journal volume & issue
Vol. 7, no. 6
pp. 693 – 700

Abstract

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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.

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