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

Roth, Beat; Jayaratna, Isuru; Sundi, Debasish; Cheng, Tiewei; Melquist, Jonathan; Choi, Woonyoung; Porten, Sima; Nitti, Giovanni; Navai, Neema; Wszolek, Matthew; Guo, Charles; Czerniak, Bogdan; McConkey, David; Dinney, Colin (2017). Employing an orthotopic model to study the role of epithelial-mesenchymal transition in bladder cancer metastasis. OncoTarget, 8(21), pp. 34205-34222. Impact Journals LLC 10.18632/oncotarget.11009

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Roth, Beat

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1949-2553

Publisher:

Impact Journals LLC

Language:

English

Submitter:

Laetitia Hayoz

Date Deposited:

01 Mar 2018 09:33

Last Modified:

04 Nov 2019 21:10

Publisher DOI:

10.18632/oncotarget.11009

PubMed ID:

27494900

Uncontrolled Keywords:

SNAIL bladder cancer circulating tumor cells metastasis orthotopic xenografts

BORIS DOI:

10.7892/boris.108826

URI:

https://boris.unibe.ch/id/eprint/108826

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