Oncotarget

Research Papers:

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

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 and Colin Dinney _

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Oncotarget. 2017; 8:34205-34222. https://doi.org/10.18632/oncotarget.11009

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Abstract

Beat Roth1,4, Isuru Jayaratna1, Debasish Sundi1, Tiewei Cheng1,3, Jonathan Melquist1, Woonyoung Choi1, Sima Porten1, Giovanni Nitti3, Neema Navai1, Matthew Wszolek1,5, Charles Guo2, Bogdan Czerniak2, David McConkey1,*, Colin Dinney1,*

1Department of Urology, MD Anderson Cancer Center, Houston, TX, USA

2Department of Pathology, MD Anderson Cancer Center, Houston, TX, USA

3The Programs in Experimental Therapeutics and Cancer Biology, The University of Texas-Graduate School of Biomedical Sciences, Houston, TX, USA

4Department of Urology, University Hospital, Bern, Switzerland

5Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

*These authors contributed equally to this work

Correspondence to:

Colin Dinney, email: cdinney@mdanderson.org

Keywords: SNAIL, metastasis, circulating tumor cells, orthotopic xenografts, bladder cancer

Received: March 17, 2016     Accepted: June 30, 2016     Published: August 02, 2016

ABSTRACT

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.


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