Ces Urol 2015, 19(4):270-280 | DOI: 10.48095/cccu2015038

Cell culture models of urothelial carcinoma chemoresistance

Michaela Kripnerová, Jiří Hatina

Ústav biologie, Lékařská fakulta UK v Plzni

Kripnerová M, Hatina J. Cell culture models of urothelial carcinoma chemoresistance. Major statement: Cancer cell lines and progression series thereof represent a crucial experimental tool to unravel basic biological mechanisms of carcinogenesis, including therapeutic response. The article gives an overview of current cell culture models of urothelial carcinoma, focusing on chemoresistance mechanisms. Urothelial bladder carcinoma is the seventh most frequent tumor type in our population. From both biological and clinical points of view, it represents a very heterogeneous group of cancers, from non-muscle-invasive superficial papillary carcinoma to muscle-invasive carcinoma as the two major subtypes. Cell culture of urothelial carcinoma is relatively feasible, with more than 50 established tumor cell lines. Most of them were derived from late stage muscle-invasive tumors. In contrast, cell lines derived from early stages and/or papillary superficial tumors are relatively scarce. Studying tumor progression is largely facilitated by use of progression cell line series - an array of several cell lines established on the same genetic background with gradually increasing transformation status. All available progression series of urothelial carcinoma cell lines have been experimentally established either by various in vitro manipulations or in vivo, following a spontaneous progression of an original cancer cell line after its introduction into a suitable host animal. An important variant of cancer cell line progression series is provided by derivation of chemoresistant daughter cell lines after administration of cytostatics to a chemosensitive parental cell line. This specific variant can substantially contribute to our understanding of various biological mechanisms of chemoresistance. An important new finding in this respect is the fact that in many if not all chemoresistant daughter cell lines, several biologically distinct chemoresistance mechanisms seem to be co-expressed. In addition to these entirely experimental applications, such chemoresistant cancer cell lines can provide valuable preclinical models to test new therapeutic options aimed at recovery of chemosensitivity.

Keywords: Cancer cell lines, chemoresistance, chemotherapy, urothelial carcinoma.

Received: August 28, 2015; Accepted: October 21, 2015; Prepublished online: October 7, 2015; Published: December 21, 2015