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. DESIGN, SETTING, AND PARTICIPANTS: 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. MEASUREMENTS: Noninvasive, sensitive bioluminescent imaging of human firefly luciferase 2-positive bladder cancer in mice using the IVIS100 imaging system. RESULTS AND LIMITATIONS: 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.
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. DESIGN, SETTING, AND PARTICIPANTS: 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. MEASUREMENTS: Noninvasive, sensitive bioluminescent imaging of human firefly luciferase 2-positive bladder cancer in mice using the IVIS100 imaging system. RESULTS AND LIMITATIONS: 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 humanbladder 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: J K Simmons; B E Hildreth; W Supsavhad; S M Elshafae; B B Hassan; W P Dirksen; R E Toribio; T J Rosol Journal: Vet Pathol Date: 2015-05-28 Impact factor: 2.221
Authors: Tran T Hoang; Komal Mandleywala; Tara Viray; Kel Vin Tan; Jason S Lewis; Patricia M R Pereira Journal: Mol Imaging Biol Date: 2022-02-11 Impact factor: 3.484
Authors: Wolfgang Jäger; Yutaka Horiguchi; Jay Shah; Tetsutaro Hayashi; Shannon Awrey; Kilian M Gust; Boris A Hadaschik; Yoshiyuki Matsui; Shawn Anderson; Robert H Bell; Susan Ettinger; Alan I So; Martin E Gleave; I-Ling Lee; Colin P Dinney; Masaaki Tachibana; David J McConkey; Peter C Black Journal: J Urol Date: 2013-03-07 Impact factor: 7.450