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Published on: September 13, 2018
The Role of FGFR3 in the Progression of Bladder Cancer
Sahoko Ninomiya1, Yukari Ishiguro1, Hisashi Hasumi1
1Department of Urology and Renal Transplantation, Yokohama City University Medical Center, Yokohama 232-0024, Japan.
Abstract:
Introduction: Bladder cancer is associated with a high recurrence rate, and outcomes for muscle-invasive and metastatic disease remain poor. New targeted therapies, such as the FGFR inhibitor erdafitinib, have been introduced, but the progression from non-muscle-invasive to muscle-invasive disease remains a major clinical challenge. Methods: In this study, we performed immunohistochemical staining for FGFR1-FGFR4 on surgical specimens from 192 cases of urothelial carcinoma. We also conducted various functional assays on human bladder cancer cell lines to assess protein/gene expression, cell proliferation, migration, invasion, and colony formation. Results: FGFR2 and FGFR3 expressions were found to be significantly down-regulated in high-grade (0.014) and muscle-invasive (0.002) tumors, respectively. Functionally, the FGFR inhibitor erdafitinib suppressed cell proliferation and migration, and FGFR3 silencing also markedly reduced proliferation, migration, invasion, and colony formation in cancer cell lines. Conclusions: The down-regulation of FGFR3 in muscle-invasive bladder cancer, coupled with the inhibitory effect of its inactivation on cell growth, suggests a significant role for FGFR3 in bladder cancer progression.
Insights
Fibroblast growth factor receptor 3 (FGFR3) is down-regulated in muscle-invasive bladder cancer. Its inactivation inhibits cancer cell growth, suggesting FGFR3 plays a key role in bladder cancer progression.
Area of Science:
- Oncology
- Urothelial Carcinoma Research
- Molecular Biology
Background:
- Bladder cancer has high recurrence rates and poor outcomes for advanced disease.
- Progression from non-muscle-invasive to muscle-invasive bladder cancer is a significant clinical challenge.
- Fibroblast growth factor receptors (FGFRs) are emerging therapeutic targets.
Purpose of the Study:
- To investigate the expression and role of FGFR1-FGFR4 in urothelial carcinoma.
- To assess the impact of FGFR inhibition on bladder cancer cell behavior.
Main Methods:
- Immunohistochemical staining of FGFR1-FGFR4 on 192 urothelial carcinoma specimens.
- Functional assays in human bladder cancer cell lines (proliferation, migration, invasion, colony formation).
- Treatment with FGFR inhibitor erdafitinib and FGFR3 gene silencing.
Main Results:
- FGFR2 and FGFR3 expression were significantly down-regulated in high-grade and muscle-invasive tumors, respectively.
- Erdafitinib suppressed bladder cancer cell proliferation and migration.
- FGFR3 silencing reduced proliferation, migration, invasion, and colony formation.
Conclusions:
- Down-regulation of FGFR3 is associated with muscle-invasive bladder cancer.
- FGFR3 inactivation inhibits bladder cancer cell growth and progression.
- FGFR3 plays a significant role in the progression of bladder cancer.
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