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Updated: May 8, 2026
3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
Published on: September 13, 2018
HDAC inhibition suppresses bladder cancer cell adhesion to collagen under flow conditions
Eva Juengel1, Sascha Meyer dos Santos, Tanja Schneider
1Department of Urology, Johann Wolfgang Goethe-University, 60590 Frankfurt am Main, Germany.
Abstract:
The influence of the histone deacetylase (HDAC)-inhibitor, valproic acid (VPA), on bladder cancer cell adhesion in vitro was investigated in this paper. TCCSUP and RT-112 bladder cancer cells were treated with VPA (0.5 or 1 mM) twice or thrice weekly for 14 days. Controls remained untreated. Tumour cell interaction with immobilized collagen was evaluated by a flow-based adhesion assay using a shear force of 2 or 4 dyne/cm(2). The effects of VPA on the integrin adhesion receptors α3, α5, β1, β3 and β4 were assessed by flow cytometry to determine integrin surface expression and by western blotting to determine the cytoplasmic integrin level. VPA of 0.5 mM and 1 mM significantly prevented binding of both RT-112 and TCCSUP cells to collagen, compared with the untreated controls. Adhesion was reduced to a higher extent when RT-112 (subjected to 2 dyne/cm(2)) or TCCSUP (subjected to 2 or 4 dyne/cm(2)) tumour cells were treated with VPA three times a week, compared to the two times a week protocol. VPA caused a significant up-regulation of the integrin α3, α5, β1, β3 and β4 subtypes on the TCCSUP cell surface membrane. In RT-112 cells, only integrin α5 was elevated on the cell surface following VPA exposure. Western blotting revealed an up-regulation of α3, α5, β3 and β4 integrins and down-regulation of the integrin β1 protein by VPA in TCCSUP. VPA also up-regulated α5 and down-regulated β1 integrin in RT-112 cells, but also reduced α3 and β3 in TCCSUP. VPA exerted adhesion-blocking properties on bladder cancer cells under physiologic flow conditions. The effects were accompanied by distinct modifications of the integrin expression profile, which differ depending on the cell lines used. Application of VPA might be an innovative option to prevent bladder cancer dissemination.
Insights
Valproic acid (VPA), a HDAC inhibitor, reduces bladder cancer cell adhesion to collagen by altering integrin expression. This suggests VPA may be a novel therapeutic strategy to prevent cancer spread.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Bladder cancer cell adhesion is crucial for metastasis.
- Histone deacetylase (HDAC) inhibitors, like valproic acid (VPA), are explored for cancer therapy.
- Integrins play a key role in cell adhesion and cancer progression.
Purpose of the Study:
- To investigate the effect of VPA on bladder cancer cell adhesion in vitro.
- To determine how VPA influences integrin expression in bladder cancer cells.
- To evaluate VPA's potential in preventing bladder cancer cell dissemination.
Main Methods:
- TCCSUP and RT-112 bladder cancer cells were treated with VPA (0.5 or 1 mM).
- Cell adhesion to collagen was assessed using a flow-based assay under shear stress.
- Integrin expression (surface and cytoplasmic levels) was analyzed by flow cytometry and western blotting.
Main Results:
- VPA significantly inhibited bladder cancer cell adhesion to collagen in a dose-dependent manner.
- Treatment frequency (twice vs. thrice weekly) impacted adhesion reduction.
- VPA altered integrin expression profiles, up-regulating several subtypes (α3, α5, β1, β3, β4) in TCCSUP cells and α5 in RT-112 cells, while down-regulating β1 in both cell lines.
Conclusions:
- VPA demonstrates adhesion-blocking properties on bladder cancer cells under physiological flow conditions.
- VPA modulates integrin expression, with cell-line-specific differences observed.
- VPA represents a potential innovative therapeutic approach to inhibit bladder cancer metastasis.
