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

doi:10.18632/oncotarget.11009

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 journal › Article › peer-review

14 Scopus citations

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 language	English (US)
Pages (from-to)	34205-34222
Number of pages	18
Journal	Oncotarget
Volume	8
Issue number	21
DOIs	https://doi.org/10.18632/oncotarget.11009
State	Published - 2017
Externally published	Yes

Keywords

Bladder cancer
Circulating tumor cells
Metastasis
Orthotopic xenografts
SNAIL

ASJC Scopus subject areas

Oncology

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10.18632/oncotarget.11009

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title = "Employing an orthotopic model to study the role of epithelialmesenchymal transition in bladder cancer metastasis",

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

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AU - Roth, Beat

AU - Jayaratna, Isuru

AU - Sundi, Debasish

AU - Cheng, Tiewei

AU - Melquist, Jonathan

AU - Choi, Woonyoung

AU - Porten, Sima

AU - Nitti, Giovanni

AU - Navai, Neema

AU - Wszolek, Matthew

AU - Guo, Charles

AU - Czerniak, Bogdan

AU - McConkey, David

AU - Dinney, Colin

N1 - Publisher Copyright: © Roth et al.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Bladder cancer

KW - Circulating tumor cells

KW - Metastasis

KW - Orthotopic xenografts

KW - SNAIL

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JO - Oncotarget

JF - Oncotarget

IS - 21

ER -

Employing an orthotopic model to study the role of epithelialmesenchymal transition in bladder cancer metastasis

Abstract

Keywords

ASJC Scopus subject areas

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