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Updated: Nov 22, 2025
3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
Published on: September 13, 2018
SLC35F2, a Transporter Sporadically Mutated in the Untranslated Region, Promotes Growth, Migration, and Invasion of
Roland Kotolloshi1, Martin Hölzer2, Mieczyslaw Gajda3
1Department of Urology, Jena University Hospital, 07740 Jena, Germany.
Abstract:
Bladder cancer is a very heterogeneous disease and the molecular mechanisms of carcinogenesis and progression are insufficiently investigated. From the DNA sequencing analysis of matched non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) samples from eight patients, we identified the tumour-associated gene SLC35F2 to be mutated in the 5' and 3' untranslated region (UTR). One mutation in 3'UTR increased the luciferase activity reporter, suggesting its influence on the protein expression of SLC35F2. The mRNA level of SLC35F2 was increased in MIBC compared with NMIBC. Furthermore, in immunohistochemical staining, we observed a strong intensity of SLC35F2 in single tumour cells and in the border cells of solid tumour areas with an atypical accumulation around the nucleus, especially in the MIBC. This suggests that SLC35F2 might be highly expressed in aggressive and invasive tumour cells. Moreover, knockdown of SLC35F2 repressed the growth of bladder cancer cells in the monolayer and spheroid model and suppressed migration and invasion of bladder cancer cells. In conclusion, we suggest that SLC35F2 is involved in bladder cancer progression and might provide a new therapeutic approach, for example, by the anti-cancer drug YM155, a cargo of the SLC35F2 transporter.
Insights
The tumor-associated gene SLC35F2 is implicated in bladder cancer progression. Mutations and increased expression correlate with invasive bladder cancer, suggesting SLC35F2 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Bladder cancer exhibits significant heterogeneity, with poorly understood molecular mechanisms of carcinogenesis and progression.
- Investigating tumor-associated genes is crucial for understanding bladder cancer development.
Purpose of the Study:
- To identify and characterize the role of the tumor-associated gene SLC35F2 in bladder cancer progression.
- To explore SLC35F2 as a potential therapeutic target for bladder cancer.
Main Methods:
- DNA sequencing of matched non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) samples.
- Luciferase reporter assays to assess the functional impact of UTR mutations.
- Quantitative mRNA analysis and immunohistochemical staining.
- In vitro cell growth, migration, and invasion assays following SLC35F2 knockdown.
Main Results:
- Mutations in the 5' and 3' untranslated regions (UTR) of SLC35F2 were identified in bladder cancer.
- A 3'UTR mutation enhanced luciferase activity, indicating altered protein expression.
- SLC35F2 mRNA levels and protein expression were elevated in MIBC compared to NMIBC, particularly in aggressive tumor cells.
- Knockdown of SLC35F2 inhibited bladder cancer cell proliferation, migration, and invasion.
Conclusions:
- SLC35F2 plays a significant role in bladder cancer progression.
- SLC35F2 is a potential biomarker for aggressive bladder cancer.
- Targeting SLC35F2, potentially with drugs like YM155, represents a novel therapeutic strategy for bladder cancer.
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