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Cryptosporidium parvum-induced ileo-caecal adenocarcinoma and Wnt signaling in a mouse model
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Limited
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036476/ https://www.ncbi.nlm.nih.gov/pubmed/24652769 http://dx.doi.org/10.1242/dmm.013292 |
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author | Benamrouz, Sadia Conseil, Valerie Chabé, Magali Praet, Marleen Audebert, Christophe Blervaque, Renaud Guyot, Karine Gazzola, Sophie Mouray, Anthony Chassat, Thierry Delaire, Baptiste Goetinck, Nathalie Gantois, Nausicaa Osman, Marwan Slomianny, Christian Dehennaut, Vanessa Lefebvre, Tony Viscogliosi, Eric Cuvelier, Claude Dei-Cas, Eduardo Creusy, Colette Certad, Gabriela |
author_facet | Benamrouz, Sadia Conseil, Valerie Chabé, Magali Praet, Marleen Audebert, Christophe Blervaque, Renaud Guyot, Karine Gazzola, Sophie Mouray, Anthony Chassat, Thierry Delaire, Baptiste Goetinck, Nathalie Gantois, Nausicaa Osman, Marwan Slomianny, Christian Dehennaut, Vanessa Lefebvre, Tony Viscogliosi, Eric Cuvelier, Claude Dei-Cas, Eduardo Creusy, Colette Certad, Gabriela |
author_sort | Benamrouz, Sadia |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4036476 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Company of Biologists Limited |
record_format | MEDLINE/PubMed |
spelling | pubmed-40364762014-07-03 Cryptosporidium parvum-induced ileo-caecal adenocarcinoma and Wnt signaling in a mouse model Benamrouz, Sadia Conseil, Valerie Chabé, Magali Praet, Marleen Audebert, Christophe Blervaque, Renaud Guyot, Karine Gazzola, Sophie Mouray, Anthony Chassat, Thierry Delaire, Baptiste Goetinck, Nathalie Gantois, Nausicaa Osman, Marwan Slomianny, Christian Dehennaut, Vanessa Lefebvre, Tony Viscogliosi, Eric Cuvelier, Claude Dei-Cas, Eduardo Creusy, Colette Certad, Gabriela Dis Model Mech Research Article 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. The Company of Biologists Limited 2014-06 2014-03-20 /pmc/articles/PMC4036476/ /pubmed/24652769 http://dx.doi.org/10.1242/dmm.013292 Text en © 2014. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Benamrouz, Sadia Conseil, Valerie Chabé, Magali Praet, Marleen Audebert, Christophe Blervaque, Renaud Guyot, Karine Gazzola, Sophie Mouray, Anthony Chassat, Thierry Delaire, Baptiste Goetinck, Nathalie Gantois, Nausicaa Osman, Marwan Slomianny, Christian Dehennaut, Vanessa Lefebvre, Tony Viscogliosi, Eric Cuvelier, Claude Dei-Cas, Eduardo Creusy, Colette Certad, Gabriela Cryptosporidium parvum-induced ileo-caecal adenocarcinoma and Wnt signaling in a mouse model |
title | Cryptosporidium parvum-induced ileo-caecal adenocarcinoma and Wnt signaling in a mouse model |
title_full | Cryptosporidium parvum-induced ileo-caecal adenocarcinoma and Wnt signaling in a mouse model |
title_fullStr | Cryptosporidium parvum-induced ileo-caecal adenocarcinoma and Wnt signaling in a mouse model |
title_full_unstemmed | Cryptosporidium parvum-induced ileo-caecal adenocarcinoma and Wnt signaling in a mouse model |
title_short | Cryptosporidium parvum-induced ileo-caecal adenocarcinoma and Wnt signaling in a mouse model |
title_sort | cryptosporidium parvum-induced ileo-caecal adenocarcinoma and wnt signaling in a mouse model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036476/ https://www.ncbi.nlm.nih.gov/pubmed/24652769 http://dx.doi.org/10.1242/dmm.013292 |
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