Receptor tyrosine kinase (RTK) signaling is altered in urothelial cancer. Namely, FGFR dependent signaling is affected [
1]. FGFR3 mutations causing ligand independent dimerization and enhanced kinase activity with constitutive FGFR3 activation are prevalent in low grade non muscle invasive transitional cell carcinoma (TCC) whereas overexpression of wild type FGFR3 is observed in muscle invasive bladder cancer [
2‐
4]. Also, aberrant expression of FGFR1, FGFR2, and FGF2 ligand has been demonstrated [
5‐
7]. Further RTKs such as VEGFR and PDGFR are involved in bladder cancer progression [
8]. Therefore, drugs for inhibition of RTKs are under investigation for the treatment of bladder cancer. Among those, TKI-258 targeting signaling of FGFR/PDGFR/VEGFR and further related RTKs is investigated as a potential anti TCC compound [
9,
10]. The affinity order for TKI-258 has been determined for different RTKs being highest for FGFR1 and FGFR3 followed by VEGFR1-3, PDGFRβ, FLT-3 and c-Kit revealing the complexity of the drug [
11]. The responsiveness towards RTK inhibitors is difficult to predict in bladder cancer [
7,
10]. Patients with non muscle invasive bladder cancer have a good outcome and only a small portion of these tumors progress to metastatic disease. Muscle-invasive TCC is more prone to become metastatic and oncological outcome is much poorer. An indicator of metastatic potential is the EMT status [
12]. EMT is associated with enhanced cell migration and metastasis revealing a more aggressive cancer type. Bladder cancer cells can strongly differ in epithelial and mesenchymal characteristics as revealed by different cadherin subtype expression patterns [
13,
14]. Cadherins are transmembrane cell adhesion proteins that are important during development and play a role in various diseases including cancer. E-cadherin is expressed in epithelial cells. E-cadherin has characteristics of a tumor suppressor that inhibits cell invasion and loss of E-cadherin is important for induction of EMT [
15]. During EMT a cadherin switch occurs. E-cadherin is replaced by N-cadherin a well established mesenchymal cell type marker in pathology [
14]. P-cadherin is a further cadherin subtype expressed in malignancies but could not yet been assigned to an epithelial or mesenchymal cell type in bladder cancer [
14,
16]. The mesenchymal marker vimentin represents an intermediate filament that replaces the epithelial cytokeratin filament [
17]. The cadherin switch involves transcriptional regulation by epithelial repressors (e.g. snail) for downregulation of E-cadherin and mesenchymal activators (e.g. β-catenin) for upregulation of N-cadherin [
18].
Interestingly, unsupervised gene cluster analysis by global gene expression profiling has demonstrated that non-muscle invasive and muscle invasive TCC fall into two distinct subgroups that identified EMT-related genes as relevant [
19‐
21]. The meaning of EMT status for drug responses towards inhibition of epidermal growth factor receptor has been reported in bladder cancer cells and revealed a relevance of E-cadherin expression [
22,
23].
Here, we characterized ten human bladder cancer cell lines with respect to expression of E-cadherin, N-cadherin and vimentin. Furthermore, we analyzed the response of these cells towards treatment with TKI-258 by proliferation/viability assay and colony formation assay. We observed that cells with epithelial characteristic had a stronger therapeutically beneficial response to TKI-258 than cells with mesenchymal characteristics. Thus, analysis of the EMT status may help to predict TKI-258 responsiveness independent of molecular analysis of RTK signaling.