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

Beat Roth | Zendy; Isuru Jayaratna | Zendy; Debasish Sundi | Zendy; Tiewei Cheng | Zendy; Jonathan Melquist | Zendy; Woonyoung Choi | Zendy; Sima P. Porten | Zendy; Giovanni Nitti | Zendy; Neema Navai | Zendy; Matthew Wszolek | Zendy; Charles C. Guo | Zendy; Bogdan Czerniak | Zendy; David J. McConkey | Zendy; Colin P. Dinney | Zendy

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

Author(s) -

Beat Roth,

Isuru Jayaratna,

Debasish Sundi,

Tiewei Cheng,

Jonathan Melquist,

Woonyoung Choi,

Sima P. Porten,

Giovanni Nitti,

Neema Navai,

Matthew Wszolek,

Charles C. Guo,

Bogdan Czerniak,

David J. McConkey,

Colin P. Dinney

Publication year - 2016

Publication title -

oncotarget

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.373

H-Index - 127

ISSN - 1949-2553

DOI - 10.18632/oncotarget.11009

Subject(s) - epithelial–mesenchymal transition , metastasis , bladder cancer , cancer research , snail , gene silencing , medicine , cancer , mesenchymal stem cell , pathology , biology , gene , ecology , biochemistry

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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