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Pathology & Oncology Research

, Volume 25, Issue 1, pp 391–399 | Cite as

Etoposide Upregulates Survival Favoring Sphingosine-1-Phosphate in Etoposide-Resistant Retinoblastoma Cells

  • Vinodh KakkasseryEmail author
  • S. Skosyrski
  • A. Lüth
  • B. Kleuser
  • M. van der Giet
  • R. Tate
  • J. Reinhard
  • A. Faissner
  • S. C. Joachim
  • N. Kociok
Original Article
  • 91 Downloads

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.

Keywords

Retinoblastoma Sphingosine-1-phosphate Chemotherapy resistance 

Notes

Acknowledgements

We thank C Gavranic, S Metzner, G Fels and N Wagner for their technical support in these experiments.

Funding

This study was supported by Jackstädt-Stiftung S 134–10.063 (V Kakkassery) and Deutsche Forschungsgemeinschaft DFG KL988/4–4 (B Kleuser).

Compliance with Ethical Standards

Conflict of Interest

None.

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Copyright information

© Arányi Lajos Foundation 2017

Authors and Affiliations

  • Vinodh Kakkassery
    • 1
    • 2
    • 3
    Email author
  • S. Skosyrski
    • 1
  • A. Lüth
    • 4
  • B. Kleuser
    • 4
  • M. van der Giet
    • 5
  • R. Tate
    • 6
  • J. Reinhard
    • 7
  • A. Faissner
    • 7
  • S. C. Joachim
    • 2
  • N. Kociok
    • 1
  1. 1.Department of OphthalmologyCharité UniversitätsmedizinBerlinGermany
  2. 2.Department of OphthalmologyRuhr-University BochumBochumGermany
  3. 3.Department of OphthalmologyUniversity RostockRostockGermany
  4. 4.Department of Nutrition ScienceUniversity PotsdamPotsdamGermany
  5. 5.Department of Nephrology, Campus Benjamin FranklinCharité UniversitätsmedizinBerlinGermany
  6. 6.Strathclyde Institute of Pharmacy and Biomedical SciencesUniversity of StrathclydeGlasgowUK
  7. 7.Department of Cell Morphology and Molecular Neurobiology, Faculty of Biology and BiotechnologyRuhr-University BochumBochumGermany

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