@article{KakkasserySkosyrskiLuethetal.2017,
  author    = {Kakkassery, Vinodh and Skosyrski, S. and L{\"u}th, A. and Kleuser, Burkhard and van der Giet, Maria and Tate, R. and Reinhard, J. and Faissner, Andreas and Joachim, Stephanie Christine and Kociok, N.},
  title     = {Etoposide Upregulates Survival Favoring Sphingosine-1-Phosphate in Etoposide-Resistant Retinoblastoma Cells},
  series = {Pathology \& Oncology Research},
  volume    = {25},
  journal   = {Pathology \& Oncology Research},
  number    = {1},
  publisher = {Springer},
  address   = {Dordrecht},
  issn      = {1219-4956},
  doi       = {10.1007/s12253-017-0360-x},
  pages     = {391 -- 399},
  year      = {2017},
  abstract  = {Improved knowledge of retinoblastoma chemotherapy resistance is needed to raise treatment efficiency. The objective of this study was to test whether etoposide alters glucosyl-ceramide, ceramide, sphingosine, and sphingosine-1-phosphate (sphingosine-1-P) levels in parental retinoblastoma cells (WERI Rb1) or their etoposide-resistant subclones (WERI EtoR). WERI Rb1 and WERI EtoR were incubated with 400 ng/ml etoposide for 24 h. Levels of glucosyl-ceramides, ceramides, sphingosine, sphingosine-1-P were detected by Q-TOF mass spectrometry. Statistical analysis was done by ANOVA followed by Tukey post-hoc test (p < 0.05). The mRNA expression of sphingolipid pathways enzymes in WERI Rb1, WERI EtoR and four human retinoblastoma tissue samples was analyzed by quantitative real-time PCR. Pathways enzymes mRNA expression confirmed similarities of human sphingolipid metabolism in both cell lines and tissue samples, but different relative expression. Significant up-regulation of sphingosine was seen in both cell lines (p < 0.001). Only sphingosine-1-P up-regulation was significantly increased in WERI EtoR (p < 0.01), but not in WERI Rb1 (p > 0.2). Both cell lines upregulate pro-apoptotic sphingosine after etoposide incubation, but only WERI EtoR produces additional survival favorable sphingosine-1-P. These data may suggest a role of sphingosine-1-P in retinoblastoma chemotherapy resistance, although this seems not to be the only resistance mechanism.},
  language  = {en}
}