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Review

What we have learned from urinary bladder cancer models

Carina Bernardo , Céu Costa , Carlos Palmeira 1,3,4 , Rosário Pinto-Leite , Paula Oliveira , Rui Freitas ,
6
1,5
1,4
1,2
7
Francisco Amado , Lúcio L. Santos 1,4,8
2
1 Experimental Pathology and Therapeutics Group-Research Center, Portuguese Oncology Institute-Porto (IPO-Porto), Rua Dr. António Bernardino
de Almeida, 4200-072 Porto, Portugal.
2
Mass Spectrometry Group, QOPNA, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
3 Department of Immunology, Portuguese Oncology Institute-Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.
4 School of Health Sciences, Fernando Pessoa University, 4249-004 Porto, Portugal.
5 Genetic Service, Cytogenetic Laboratory, Hospital Center of Trás-os-Montes e Alto Douro, 5000-508 Vila Real, Portugal.
6 Department of Veterinary Sciences, CITAB, University of Trás-os-Montes e Alto Douro, 5001-801 Vila Real, Portugal.
7 Department of Urology, Portuguese Oncology Institute-Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.
8 Department of Surgical Oncology, Portuguese Oncology Institute-Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, 4200-072 Porto,
Portugal.
Correspondence to: Dr. Lúcio L. Santos, Portuguese Oncology Institute-Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, 4200-072
Porto, Portugal. E-mail: llarasantos@gmail.com
A B S T R AC T
Urinary bladder cancer (UBC) is a heterogeneous disease with highly variable clinical outcomes and responses to chemotherapy.
Despite some advances in the molecular understanding of UBC, this knowledge still has not been translated to the clinic in terms of
improvements in the prognosis and treatment of patients. Suitable urinary bladder tumor models representative of the human disease in
terms of histology and behavior are needed to study factors involved in tumor initiation, progression and metastasis. Further, accurate model
systems would facilitate identification of new therapeutic targets and predictive markers that could lead to optimization of existing therapies
and development of new ones. Many established cancer cell lines derived from human urinary bladder tumors representing different grades
and stages have been used as experimental models for UBC study. These cell lines reflect some of the genetic and morphologic alterations
observed in human urothelial carcinoma and serve as simplified models to study the behavior of cancer cells in vitro. However, their
translational potential is limited due to the artificial conditions, in which the cells are maintained, grown and tested. Animal models offer
a more complex and realistic model for the establishment, development, and progression of tumors as well as to evaluate new therapeutic
approaches. Over the years, the authors' group has worked with several UBC cell lines, established and characterized chemically induced
UBC models, and patient-derived xenografts models. In this study, the authors will provide a summary of the UBC models developed by
their group, analyze their translational potential and weaknesses, and define areas that remain to be explored.

Key words: Animal models; cell lines; tumor behavior; urothelial bladder cancer; xenografts

INTRODUCTION urveillance, repeated relapses, and chemoresistance makes
UBC the malignancy with the highest lifetime treatment
Urinary bladder cancer (UBC) is a heterogeneous disease cost per patient. Patient treatment and surveillance are
[2]
in terms of histopathology and clinical behavior. Around typically based on tumor histopathological features, such
70% of the patients are diagnosed with non-muscle-invasive as histologic type, differentiation degree and anatomical
bladder cancer (NMIBC) that often recur and, in about 10- extent of the disease. However, it is still challenging to
30% of the cases progress to invasive disease despite local
therapy. The remaining 30% are muscle-invasive bladder predict the risk of recurrence and progression for individual
cancer (MIBC) at presentation and are associated with patients and to identify which patients will significantly
high risk of metastasis and progression even after radical benefit from adjuvant and/or neoadjuvant chemotherapy.
surgery and systemic treatment. The necessity of lifelong
[1]
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How to cite this article: Bernardo C, Costa C, Palmeira C, Pinto-Leite R,
Oliveira P, Freitas R, Amado F, Santos LL. What we have learned from
DOI: urinary bladder cancer models. J Cancer Metastasis Treat 2016;2:51-8.
10.4103/2394-4722.171279
Received: 22-07-2015; Accepted: 02-11-2015.

© 2016 Journal of Cancer Metastasis and Treatment ¦ Published by OAE Publishing Inc. 51