title: Employing an orthotopic model to study the role of epithelial-mesenchymal 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.
authors: Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.|Department of Urology, University Hospital, Bern, Switzerland.
authors: Beat
authors: B
authors: Roth
authors: Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.
authors: Isuru
authors: I
authors: Jayaratna
authors: Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.
authors: Debasish
authors: D
authors: Sundi
authors: Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.|The Programs in Experimental Therapeutics and Cancer Biology, The University of Texas-Graduate School of Biomedical Sciences, Houston, TX, USA.
authors: Tiewei
authors: T
authors: Cheng
authors: Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.
authors: Jonathan
authors: J
authors: Melquist
authors: Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.
authors: Woonyoung
authors: W
authors: Choi
authors: Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.
authors: Sima
authors: S
authors: Porten
authors: The Programs in Experimental Therapeutics and Cancer Biology, The University of Texas-Graduate School of Biomedical Sciences, Houston, TX, USA.
authors: Giovanni
authors: G
authors: Nitti
authors: Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.
authors: Neema
authors: N
authors: Navai
authors: Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.|Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors: Matthew
authors: M
authors: Wszolek
authors: Department of Pathology, MD Anderson Cancer Center, Houston, TX, USA.
authors: Charles
authors: C
authors: Guo
authors: Department of Pathology, MD Anderson Cancer Center, Houston, TX, USA.
authors: Bogdan
authors: B
authors: Czerniak
authors: Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.
authors: David
authors: D
authors: McConkey
authors: Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.
authors: Colin
authors: C
authors: Dinney
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000073336:Whole Genome Sequencing
chemical_list: D000071250:Snail Family Transcription Factors; D016212:Transforming Growth Factor beta
keywords: SNAIL; bladder cancer; circulating tumor cells; metastasis; orthotopic xenografts