HDAC inhibition suppresses bladder cancer cell adhesion to collagen under flow conditions.

Exp Biol Med (Maywood) 2013 Nov 4;238(11):1297-304. Epub 2013 Sep 4.

Department of Urology, Johann Wolfgang Goethe-University, 60590 Frankfurt am Main, Germany.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1177/1535370213498975DOI Listing
November 2013
48 Reads

Publication Analysis

Top Keywords

bladder cancer
20
β3 β4
12
α3 α5
12
vpa
11
cells treated
8
β1 β3
8
cancer cells
8
flow conditions
8
α5 β1
8
cell adhesion
8
integrin
8
treated vpa
8
times week
8
cell surface
8
rt-112 cells
8
tccsup vpa
8
western blotting
8
cancer cell
8
cell
6
tccsup
6

References

(Supplied by CrossRef)

Vallo S et al.
Anticancer Drugs 2011

Savage B et al.
Blood 1999

Liebert M et al.
Am J Pathol 1994

Laidler P et al.
Acta Biochim Pol 2000

Similar Publications