Abstract
Urogenital schistosomiasis (infection with Schistosoma haematobium) is a major cause of bladder carcinogenesis. However, the exact mechanisms of the sequelae leading up to the development of bladder cancer are poorly understood, mainly because of a dearth of tractable mouse models. We developed a mouse model of urogenital schistosomiasis through intramural injection of parasite eggs into the bladder wall to mimic the trapping of parasite eggs in the bladder. This approach recapitulates many of the sequelae observed in infected humans. Here, we describe procedures for utilizing this surgical technique in combination with well-established transgenic mouse strains to dissect the role of cancer-related genes in the initiation and establishment of bladder carcinogenesis. The described method utilizes CRE-mediated flox activity to render mice p53 haploinsufficient before challenging them with bladder wall egg injection. These techniques are potentially amenable to studying the role of other pro-carcinogenic and cancer suppressor gene(s) in urogenital schistosomiasis-associated urothelial carcinogenesis.
This is a preview of subscription content, log in via an institution.
References
IARC (1994) Monograph on the evaluation of carcinogenic risks to humans: schistosomes, liver flukes and helicobacter pylori. WHO: International Agency for Research on Cancer 61:9–175
Khaled H (2013) Schistosomiasis and cancer in Egypt: review. J Adv Res 4(5):461–466. doi:10.1016/j.jare.2013.06.007
Conti SL, Honeycutt J, Odegaard JI et al (2015) Alterations in DNA methylation may be the key to early detection and treatment of schistosomal bladder cancer. PLoS Negl Trop Dis 9(6):e0003696. doi:10.1371/journal.pntd.0003696
Chung KT (2013) The etiology of bladder cancer and its prevention. J Cancer Sci Ther 5(10):346–361. doi:10.4172/1948-5956.1000226
Rosin MP, Saad el Din Zaki S, Ward AJ et al (1994) Involvement of inflammatory reactions and elevated cell proliferation in the development of bladder cancer in schistosomiasis patients. Mutat Res 305(2):283–292
Colley DG, Secor WE (2014) Immunology of human schistosomiasis. Parasite Immunol 36(8):347–357. doi:10.1111/pim.12087
Odegaard JI, Hsieh MH (2014) Immune responses to Schistosoma haematobium infection. Parasite Immunol 36(9):428–438. doi:10.1111/pim.12084
Honeycutt J, Hammam O, Hsieh MH (2015) Schistosoma haematobium egg-induced bladder urothelial abnormalities dependent on p53 are modulated by host sex. Exp Parasitol 158:55–60. doi:10.1016/j.exppara.2015.07.002
Rinaldi G, Young ND, Honeycutt JD et al (2015) New research tools for urogenital Schistosomiasis. J Infect Dis 211(6):861–869. doi:10.1093/infdis/jiu527
Honeycutt J, Hammam O, CL F et al (2014) Controversies and challenges in research on urogenital schistosomiasis-associated bladder cancer. Trends Parasitol 30(7):324–332. doi:10.1016/j.pt.2014.05.004
Fu C-L, Odegaard JI, Herbert DBR et al (2012) A novel mouse model of Schistosoma haematobium egg-induced immunopathology. PLoS Pathog 8:e1002605. doi:10.1371/journal.ppat.1002605
Fu CL, Apelo CA, Torres B et al (2011) Mouse bladder wall injection. J Vis Exp (53):e2523. doi:10.3791/2523
Richardson ML, CL F, Pennington LF et al (2014) A new mouse model for female genital schistosomiasis. PLoS Negl Trop Dis 8(5):e2825. doi:10.1371/journal.pntd.0002825
Harding SD, Armit C, Armstrong J et al (2011) The GUDMAP database—an online resource for genitourinary research. Development 138(13):2845–2853. doi:10.1242/dev.063594
Tucker MS, Karunaratne LB, Lewis FA et al (2013) Schistosomiasis. Curr Protoc Immuno 103:Unit 19.1. doi:10.1002/0471142735.im1901s103
Botros SS, Hammam OA, El-Lakkany NM et al (2008) Schistosoma haematobium (Egyptian strain): rate of development and effect of praziquantel treatment. J Parasitol 94:386–394. doi:10.1645/GE-1270.1
Le TL, Boyett DM, Hurley-Novatny A et al (2015) Hamster weight patterns predict the intensity and course of Schistosoma haematobium infection. J Parasitol 101(5):542–548. doi:10.1645/14-600
Acknowledgments
This work was supported by NIH R56AI119168. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the funders. The funders had no role in the preparation of the manuscript and the decision to publish. We appreciate the significant contributions by the previous Hsieh laboratory members and collaborators in the described projects, including but not limited to Chi-Ling Fu, Jared Honeycutt, Justin Odegaard, Olfat Hamman, and De’Broski R. Herbert.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Science+Business Media LLC
About this protocol
Cite this protocol
Mbanefo, E.C., Hsieh, M.H. (2018). Defining the Pathways of Urogenital Schistosomiasis-Associated Urothelial Carcinogenesis through Transgenic and Bladder Wall Egg Injection Models. In: Schulz, W., Hoffmann, M., Niegisch, G. (eds) Urothelial Carcinoma. Methods in Molecular Biology, vol 1655. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7234-0_6
Download citation
DOI: https://doi.org/10.1007/978-1-4939-7234-0_6
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-7233-3
Online ISBN: 978-1-4939-7234-0
eBook Packages: Springer Protocols