Abstract
Purpose
The study was to develop an auto-bioluminescent urinary bladder cancer (UBC) xenograft animal model for pre-clinical research.
Procedure
The study used a humanized, bacteria-originated lux reporter system consisting of six (luxCDABEfrp) genes to express components required for producing bioluminescent signals in human UBC J82, J82-Ras, and SW780 cells without exogenous substrates. Immune-deficient nude mice were inoculated with Lux-expressing UBC cells to develop auto-bioluminescent xenograft tumors that were monitored by imaging and physical examination.
Results
Lux-expressing auto-bioluminescent J82-Lux, J82-Ras-Lux, and SW780-Lux cell lines were established. Xenograft tumors derived from tumorigenic Lux-expressing auto-bioluminescent J82-Ras-Lux cells allowed a serial, non-invasive, real-time monitoring by imaging of tumor development prior to the presence of palpable tumors in animals.
Conclusions
Using Lux-expressing auto-bioluminescent tumorigenic cells enabled us to monitor the entire course of xenograft tumor development through tumor cell implantation, adaptation, and growth to visible/palpable tumors in animals.
References
Kim J-B, Urban K, Cochran E, et al. (2010) Non-invasive detection of a small number of bioluminescent cancer cells in vivo. PLoS One 5:e9364
Close DM, Patterson SS, Ripp S, et al. (2010) Autonomous bioluminescent expression of the bacterial luciferase Gene cassette ( lux ) in a mammalian cell line. PLoS One 5:e12441
Close DM, Xu T, Sayler GS, Ripp S (2011) In vivo bioluminescent imaging (BLI): noninvasive visualization and interrogation of biological processes in living animals. Sensors 11:180–206
Xu T, Ripp S, Sayler GS, Close DM (2014) Expression of a humanized viral 2 A-mediated lux operon efficiently generates autonomous bioluminescence in human cells. PLoS One 9:e96347
Buyru N, Tigli H, Ozcan F, Dalay N (2003) Ras oncogene mutations in urine sediments of patients with bladder cancer. J Biochem Mol Biol 36:399–402
Choudhary S, Wang H-CR (2007) Proapoptotic ability of oncogenic H-Ras to facilitate apoptosis induced by histone deacetylase inhibitors in human cancer cells. Mol Cancer Ther 6:1099–1111
Choudhary S, Sood S, Donnell RL, Wang H-CR (2012) Intervention of human breast cell carcinogenesis chronically induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. Carcinogenesis 33:876–885
Goel HL, Mercurio AM (2013) VEGF targets the tumour cell. Nat Rev Cancer 13:871–882
Maes W, Deroose C, Reumers V, et al. (2009) In vivo bioluminescence imaging in an experimental mouse model for dendritic cell based immunotherapy against malignant glioma. J Neuro-Oncol 91:127–139
Cui K, Xu X, Zhao H, Wong STC (2008) A quantitative study of factors affecting in vivo bioluminescence imaging. Luminescence 23:292–295
Zinn KR, Chaudhuri TR, Szafran AA, et al. (2008) Noninvasive bioluminescence imaging in small animals. ILAR 49:103–115
Vo-Dinh T (2003) Biomedical photonics handbook. CRC Press
Acknowledgments
This work was supported by the National Institutes of Health [CA177834 to H-CR W] and the University of Tennessee, College of Veterinary Medicine, Center of Excellence in Livestock Diseases and Human Health [H-CR W]. We are grateful to Ms. M Bailey for the textual editing of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethics Statement
All animal procedures were approved by the University of Tennessee Animal Care and Use Committee and were in accordance with the NIH Guide for the Care and Use of Laboratory Animals.
Conflict of Interest
SR is an author of US patent #7,300,792, Lux expression in eukaryotic cells and is a board member of 490 BioTech, Inc. BAJ, TX, and H-CRW declare that they have no competing interests.
Rights and permissions
About this article
Cite this article
John, B.A., Xu, T., Ripp, S. et al. A Real-Time Non-invasive Auto-bioluminescent Urinary Bladder Cancer Xenograft Model. Mol Imaging Biol 19, 10–14 (2017). https://doi.org/10.1007/s11307-016-0989-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11307-016-0989-y