Employing an orthotopic model to study the role of epithelialmesenchymal 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, Colin Dinney

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)34205-34222
Number of pages18
JournalOncotarget
Volume8
Issue number21
DOIs
StatePublished - Jan 1 2017

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Keywords

  • Bladder cancer
  • Circulating tumor cells
  • Metastasis
  • Orthotopic xenografts
  • SNAIL

ASJC Scopus subject areas

  • Oncology

Cite this

Roth, B., Jayaratna, I., Sundi, D., Cheng, T., Melquist, J., Choi, W., Porten, S., Nitti, G., Navai, N., Wszolek, M., Guo, C., Czerniak, B., McConkey, D., & Dinney, C. (2017). Employing an orthotopic model to study the role of epithelialmesenchymal transition in bladder cancer metastasis. Oncotarget, 8(21), 34205-34222. https://doi.org/10.18632/oncotarget.11009