1. Employing an orthotopic model to study the role of epithelial-mesenchymal transition in bladder cancer metastasis
- Author
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David J. McConkey, Giovanni Nitti, Neema Navai, Bogdan Czerniak, Tiewei Cheng, Colin P.N. Dinney, Debasish Sundi, Jonathan Melquist, Isuru Jayaratna, Sima P. Porten, Beat Roth, Charles C. Guo, Woonyoung Choi, and Matthew F. Wszolek
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,610 Medicine & health ,Snail ,circulating tumor cells ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Circulating tumor cell ,Transforming Growth Factor beta ,Cell Line, Tumor ,biology.animal ,medicine ,metastasis ,Animals ,Humans ,Gene silencing ,Epithelial–mesenchymal transition ,Neoplasm Metastasis ,Bladder cancer ,Whole Genome Sequencing ,biology ,SNAIL ,business.industry ,Gene Expression Profiling ,Transforming growth factor beta ,Neoplastic Cells, Circulating ,medicine.disease ,Primary tumor ,Disease Models, Animal ,Disease Progression ,Gene Expression Regulation, Neoplastic ,Neoplastic Cells, Circulating/metabolism ,Neoplastic Cells, Circulating/pathology ,Signal Transduction/drug effects ,Snail Family Transcription Factors/genetics ,Snail Family Transcription Factors/metabolism ,Transforming Growth Factor beta/genetics ,Transforming Growth Factor beta/metabolism ,Urinary Bladder Neoplasms/genetics ,Urinary Bladder Neoplasms/metabolism ,Urinary Bladder Neoplasms/pathology ,bladder cancer ,orthotopic xenografts ,3. Good health ,030104 developmental biology ,Urinary Bladder Neoplasms ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Snail Family Transcription Factors ,business ,Research Paper ,Signal Transduction - 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.
- Published
- 2017
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