Blocking integrin β1 decreases adhesion in chemoresistant urothelial cancer cell lines

Vallo,Stefan; Rutz,Jochen; Kautsch,Miriam; Winkelmann,Ria; Michaelis,Martin; Wezel,Felix; Bartsch,Georg; Haferkamp,Axel; Rothweiler,Florian; Blaheta,Roman   A.; Cinatl Jr,Jindrich

doi:10.3892/ol.2017.6883

Blocking integrin β1 decreases adhesion in chemoresistant urothelial cancer cell lines

Authors:
- Stefan Vallo
- Jochen Rutz
- Miriam Kautsch
- Ria Winkelmann
- Martin Michaelis
- Felix Wezel
- Georg Bartsch
- Axel Haferkamp
- Florian Rothweiler
- Roman A. Blaheta
- Jindrich Cinatl Jr
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Affiliations: Institute of Medical Virology, University Hospital Frankfurt, D-60596 Frankfurt am Main, Germany, Department of Urology, University Hospital Frankfurt, D-60596 Frankfurt am Main, Germany, Dr. Senckenberg Institute of Pathology, University Hospital Frankfurt, D-60596 Frankfurt am Main, Germany, School of Biosciences, University of Kent, Canterbury CT2 7NZ, UK, Department of Urology, University Hospital Ulm, D-89081 Ulm, Germany
Published online on: September 4, 2017 https://doi.org/10.3892/ol.2017.6883
Pages: 5513-5518

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Abstract

Treatment failure in metastatic bladder cancer is commonly caused by acquisition of resistance to chemotherapy in association with tumor progression. Since alterations of integrins can influence the adhesive and invasive behaviors of urothelial bladder cancer cell lines, the present study aimed to evaluate the role of integrins in bladder cancer cells with acquired resistance to standard first‑line chemotherapy with gemcitabine, and cisplatin. Therefore, four gemcitabine‑ and four cisplatin‑resistant sublines out of a panel of four parental urothelial bladder cancer cell lines (TCC‑SUP, HT1376, T24, and 5637) were used. Expression of integrin subunits α3, α5, α6, β1, β3, and β4 was detected using flow cytometry. Adhesion and chemotaxis were analyzed. For functional assays, integrin β1 was attenuated with a blocking antibody. In untreated cells, chemotaxis was upregulated in 3/4 gemcitabine‑resistant sublines. In cisplatin‑resistant cells, chemotaxis was enhanced in 2/4 cell lines. Acquired chemoresistance induced the upregulation of integrin β1 in all four tested gemcitabine‑resistant sublines, as well as an upregulation in 3/4 cisplatin‑resistant sublines compared with parental cell lines. Following the inhibition of integrin β1, adhesion to extracellular matrix components was downregulated in 3/4 gemcitabine‑resistant sublines and in all four tested cisplatin‑resistant sublines. Since integrin β1 is frequently upregulated in chemoresistant urothelial cancer cell lines and inhibition of integrin β1 may influence adhesion, further studies are warranted to evaluate integrin β1 as a potential therapeutic target for bladder cancer in vivo.

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