title: Real-time cancer cell tracking by bioluminescence in a preclinical model of human bladder cancer growth and metastasis.
abstract: BACKGROUND
  Bladder cancer is the fifth most common malignancy in the Western world and the second most frequently diagnosed genitourinary tumor. In the majority of cases, death from bladder cancer results from metastatic disease. Understanding the multistep process of carcinogenesis and metastasis in urothelial cancers is pivotal to the development of new therapeutic strategies. Molecular imaging of cancer growth and metastasis in preclinical models provides the essential link between cell-based experiments and clinical translation.
  
  
  OBJECTIVE
  Develop preclinical models for sensitive bladder cancer cell tracking during tumor progression and metastasis.
  
  
  METHODS
  A human transitional cell carcinoma UM-UC-3 cell line was generated that stably expresses luciferase 2 (UM-UC-3luc2), a mammalian codon-optimized firefly luciferase with superior expression. Preclinical models were developed with human UM-UC-3luc2 cells xenografted into the bladder (orthotopic model with metastases) or inoculated into the left cardiac ventricle (bone metastasis model) of immunocompromised mice.
  
  
  METHODS
  Noninvasive, sensitive bioluminescent imaging of human firefly luciferase 2-positive bladder cancer in mice using the IVIS100 imaging system.
  
  
  CONCLUSIONS
  In the orthotopic model (intravesical inoculation), tumor growth could be followed directly after inoculation of UM-UC-3luc2 cells. Importantly, micrometastatic lesions originating from orthotopically implanted cancer cells could be detected in the locoregional lymph nodes and in distant organs. In addition, the superior bioluminescent indicator firefly luciferase 2 allows the detection and monitoring of micrometastatic lesions in real time after intracardiac inoculation of human bladder cancer cells in mice. The main disadvantage is the lack of T-cell immunity in the preclinical models.
  
  
  CONCLUSIONS
  The new bioluminescence-based preclinical bladder cancer models enable superior, noninvasive, and real-time tracking of cancer cells, tumor progression, and micrometastasis. Because of the significant improvement in detection of small cell numbers, the presented models are ideally suited for functional studies dealing with minimal residual disease as well as real-time imaging of drug response.
authors: Department of Urology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Geertje
authors: G
authors: van der Horst
authors: Joost J
authors: JJ
authors: van Asten
authors: Anne
authors: A
authors: Figdor
authors: Christel
authors: C
authors: van den Hoogen
authors: Henry
authors: H
authors: Cheung
authors: Rob F M
authors: RF
authors: Bevers
authors: Rob C M
authors: RC
authors: Pelger
authors: Gabri
authors: G
authors: van der Pluijm