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

被引：16

作者：

Roth, Beat ^{[1
,5
]}

Jayaratna, Isuru ^{[1
]}

Sundi, Debasish ^{[1
]}

Cheng, Tiewei ^{[1
,3
,4
]}

Melquist, Jonathan ^{[1
]}

Choi, Woonyoung ^{[1
]}

Porten, Sima ^{[1
]}

Nitti, Giovanni

Navai, Neema ^{[1
]}

Wszolek, Matthew ^{[1
,6
]}

Guo, Charles ^{[2
]}

Czerniak, Bogdan ^{[2
]}

McConkey, David ^{[1
]}

Dinney, Colin ^{[1
]}

机构：

[1] MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA

[2] MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA

[3] Univ Texas Houston, Grad Sch Biomed Sci, Program Expt Therapeut, Houston, TX USA

[4] Univ Texas Houston, Grad Sch Biomed Sci, Programs Canc Biol, Houston, TX USA

[5] Univ Hosp Bern, Dept Urol, Bern, Switzerland

[6] Harvard Med Sch, Massachusetts Gen Hosp, Dept Urol, Boston, MA USA

来源：

ONCOTARGET | 2017年 / 8卷 / 21期

关键词：

SNAIL; metastasis; circulating tumor cells; orthotopic xenografts; bladder cancer; CIRCULATING TUMOR-CELLS; RADICAL CYSTECTOMY; EXPRESSION; CARCINOMA; IMPLANTATION; PROSTATE; GROWTH; MIGRATION; DISPLAY; PROTEIN;

D O I：

10.18632/oncotarget.11009

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 TGF beta 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.

引用

页码：34205 / 34222

页数：18

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