Modeling human bladder cancer
Bladder cancer is a major public health concern and the treatment options available are unable to significantly prevent disease recurrence and progression. The need for experimental tumor models to efficiently reproduce the pathology of human cancers has prompted researchers to attempt various approaches.
A PubMed search combining the MeSH bladder cancer and models was executed in March 2017.
We review the advantages and limitations of currently available in vitro 2D and 3D bladder cancer models as well as in vivo rodent models. To date, despite the description of a variety of animal models (including transplantable, carcinogen-induced and genetically engineered models), the establishment of reliable, simple, practicable and reproducible animal models remains an ongoing challenge. Recently, sophisticated 3D culture systems have been designed to better recapitulate the phenotypic and cellular heterogeneity as well as microenvironmental aspects of in vivo tumor growth, while being more flexible to conduct repeated experiments.
Selecting the most appropriate model for a specific application will maximize the conversion of potential therapies from the laboratory to clinical practice and requires an understanding of the various models available.
KeywordsBladder cancer Animal models 3D models
We thank Stéphane Chabaud for carefully reading the manuscript. This work was supported by Bladder Cancer Canada Grant to FP and CRG and Ferring Grant to SB. CRG is the recipient of an FRQS Doctoral Research award. FP is the recipient of FRQS Scholarship. SB is the recipient of Canadian Urological Association Scholarship Funds and Canadian Institute for Health Research Grant #258229.
CRG completed the preparation of table and wrote the manuscript that has been corrected and revised by SB and FP.
Compliance with ethical standards
Conflict of interest
The authors declare that there is no conflict of interest regarding the publication of this paper.
- 5.Druckey H (1964) Selective induction of bladder cancer in rats by dibutyl- and N-butyl-N-butanol(4)- nitrosamine. ZeitschriftKrebsforschung 66:280–290Google Scholar
- 13.Voskoglou-Nomikos T, Pater JL, Seymour L (2003) Clinical predictive value of the in vitro cell line. Human Xenograft Mouse Allograft Preclin Cancer Models 9:4227–4239Google Scholar
- 14.Domingos-Pereira S, Cesson V, Chevalier MF et al (2016) Preclinical efficacy and safety of the Ty21a vaccine strain for intravesical immunotherapy of non-muscle-invasive bladder cancer. OncoImmunology 6:e1265720–e1265727. https://doi.org/10.1080/2162402X.2016.1265720 CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Zhang Z-T, Pak J, Shapiro E et al (1999) Urothelium-specific expression of an oncogene in transgenic mice induced the formation of carcinoma. Can Res 59:3512–3517Google Scholar
- 19.Cheng J, Huang H, Zhang Z-T et al (2002) Overexpression of epidermal growth factor receptor in urothelium elicits urothelial hyperplasia and promotes bladder tumor growth. Can Res 62:4157–4163Google Scholar
- 27.Hennessey PT, Ochs MF, Mydlarz WW et al (2011) Promoter methylation in head and neck squamous cell carcinoma cell lines is significantly different than methylation in primary tumors and xenografts. PLoS One 6:e20584–e20587. https://doi.org/10.1371/journal.pone.0020584 CrossRefPubMedPubMedCentralGoogle Scholar
- 33.Knuchel R, Hofstädter F, Jenkins WEA, Masters JRW (1989) Sensitivities of monolayers and spheroids of the human bladder cancer cell line mgh-u1 to the drugs used for intravesical chemotherapy. Can Res 49:1397–1401Google Scholar
- 40.Wang L-S, Boulaire J, Chan PPY et al (2010) The role of stiffness of gelatin-hydroxyphenylpropionic acid hydrogels formed by enzyme-mediated crosslinking on the differentiation of human mesenchymal stem cell. Biomaterials 31:8608–8616. https://doi.org/10.1016/j.biomaterials.2010.07.075 CrossRefPubMedGoogle Scholar
- 55.Ringuette-Goulet C, Bernard G, Chabaud S et al (2017) Tissue-engineered human 3D model of bladder cancer for invasion study and drug discovery. Biomaterials 145:233–241. https://doi.org/10.1016/j.biomaterials.2017.08.041 CrossRefPubMedGoogle Scholar
- 60.Jeong S-Y, Lee J-H, Shin Y et al (2016) Co-culture of tumor spheroids and fibroblasts in a collagen matrix-incorporated microfluidic chip mimics reciprocal activation in solid tumor microenvironment. PLoS One 11:e0159013–e0159017. https://doi.org/10.1371/journal.pone.0159013 CrossRefPubMedPubMedCentralGoogle Scholar