Employing an orthotopic model to study the role of epithelial-mesenchymal transition in bladder cancer metastasis

Epithelial-to-mesenchymal transition (EMT) has been implicated in the progression of bladder cancer. To study its contribution to bladder cancer metastasis, we established new xenograft models derived from human bladder cancer cell lines utilizing an orthotopic "recycling" technique that allowed us to isolate and examine the primary tumor and its corresponding circulating tumor cells (CTC's) and metastatic lesions. Using whole genome mRNA expression profiling, we found that a reversible epithelial-to-mesenchymal transition (EMT) characterized by TGFβ pathway activation and SNAIL expression was associated with the accumulation of CTCs. Finally, we observed that conditional silencing of SNAIL completely blocked CTC production and regional/distant metastasis. Using this unique bladder cancer xenograft model, we conclude that metastasis is dependent on a reversible EMT mediated by SNAIL.

Oncotarget. 2016 Aug 02 [Epub ahead of print]

Beat Roth, Isuru Jayaratna, Debasish Sundi, Tiewei Cheng, Jonathan Melquist, Woonyoung Choi, Sima Porten, Giovanni Nitti, Neema Navai, Matthew Wszolek, Charles Guo, Bogdan Czerniak, David McConkey, Colin Dinney

Department of Urology, MD Anderson Cancer Center, Houston, Texas, USA., Department of Urology, MD Anderson Cancer Center, Houston, Texas, USA., Department of Urology, MD Anderson Cancer Center, Houston, Texas, USA., Department of Urology, MD Anderson Cancer Center, Houston, Texas, USA., Department of Urology, MD Anderson Cancer Center, Houston, Texas, USA., Department of Urology, MD Anderson Cancer Center, Houston, Texas, USA., Department of Urology, MD Anderson Cancer Center, Houston, Texas, USA., The Programs in Experimental Therapeutics and Cancer Biology, The University of Texas-Graduate School of Biomedical Sciences, TX, Houston, USA., Department of Urology, MD Anderson Cancer Center, Houston, Texas, USA., Department of Urology, MD Anderson Cancer Center, Houston, Texas, USA., Department of Pathology, MD Anderson Cancer Center, Houston, Texas, USA., Department of Pathology, MD Anderson Cancer Center, Houston, Texas, USA., Department of Urology, MD Anderson Cancer Center, Houston, Texas, USA., Department of Urology, MD Anderson Cancer Center, Houston, Texas, USA.