Impact of spheroid culture on molecular and functional characteristics of bladder cancer cell lines

Takahiro Yoshida; Nikolai A Sopko; Max Kates; Xiaopu Liu; Gregory Joice; David J Mcconkey; Trinity J Bivalacqua

doi:10.3892/ol.2019.10786

Impact of spheroid culture on molecular and functional characteristics of bladder cancer cell lines

Oncol Lett. 2019 Nov;18(5):4923-4929. doi: 10.3892/ol.2019.10786. Epub 2019 Aug 29.

Authors

Takahiro Yoshida¹, Nikolai A Sopko¹, Max Kates^{1

2}, Xiaopu Liu¹, Gregory Joice¹, David J Mcconkey^{1

2}, Trinity J Bivalacqua^{1

2}

Affiliations

¹ The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
² The Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD 21287, USA.

Abstract

The three-dimensional cell culture system is an increasingly important technique for discovering new biological aspects of cancer cells. In the present study it was demonstrated that bladder cancer cell lines, RT4 and 5637, spontaneously formed round multicellular spheroids (MCSs) in suspension by the aggregation method. MCSs consisted of cells differentially expressing luminal/basal markers. Western blotting showed that PPARγ and forkhead box A1 (FOXA1)of luminal markers were expressed to a lesser extent in MCSs than in parental cells grown in two-dimensional (2D) adherent culture. Cells in MCSs in suspension proliferated less efficiently, and were more resistant to cisplatin (CDDP) and gemcitabine than parental cells grown in 2D culture. Culturing cell lines as MCSs in suspension is a notable platform to decipher alternative biological aspects of bladder cancer cells, which could not be unraveled by the conventional 2D adherent culture.

Keywords: bladder cancer; cell culture; cell line; chemosensitivity; molecular subtype; multicellular spheroid.