Etoposide upregulates survival favoring sphingosine-1-phosphate in etoposide-resistant retinoblastoma cells

Vinodh Kakkassery, S. Skosyrski, A. Lüth, B. Kleuser, M. van der Giet, R. Tate, J. Reinhard, A. Faissner, S. C. Joachim, N. Kociok

Research output: Contribution to journalArticle

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.

LanguageEnglish
Number of pages9
JournalPathology & Oncology Research
Early online date15 Nov 2017
DOIs
Publication statusE-pub ahead of print - 15 Nov 2017

Fingerprint

Sphingosine
Retinoblastoma
Etoposide
Up-Regulation
Glucosylceramides
Ceramides
Drug Therapy
sphingosine 1-phosphate
Mass Spectrometry
Analysis of Variance
Cell Line

Keywords

  • retinoblastoma
  • sphingosine-1-phosphate
  • chemotherapy resistance

Cite this

Kakkassery, Vinodh ; Skosyrski, S. ; Lüth, A. ; Kleuser, B. ; van der Giet, M. ; Tate, R. ; Reinhard, J. ; Faissner, A. ; Joachim, S. C. ; Kociok, N. / Etoposide upregulates survival favoring sphingosine-1-phosphate in etoposide-resistant retinoblastoma cells. In: Pathology & Oncology Research. 2017.
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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.",
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Kakkassery, V, Skosyrski, S, Lüth, A, Kleuser, B, van der Giet, M, Tate, R, Reinhard, J, Faissner, A, Joachim, SC & Kociok, N 2017, 'Etoposide upregulates survival favoring sphingosine-1-phosphate in etoposide-resistant retinoblastoma cells' Pathology & Oncology Research. https://doi.org/10.1007/s12253-017-0360-x

Etoposide upregulates survival favoring sphingosine-1-phosphate in etoposide-resistant retinoblastoma cells. / Kakkassery, Vinodh; Skosyrski, S.; Lüth, A.; Kleuser, B.; van der Giet, M.; Tate, R.; Reinhard, J.; Faissner, A.; Joachim, S. C.; Kociok, N.

In: Pathology & Oncology Research, 15.11.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Etoposide upregulates survival favoring sphingosine-1-phosphate in etoposide-resistant retinoblastoma cells

AU - Kakkassery, Vinodh

AU - Skosyrski, S.

AU - Lüth, A.

AU - Kleuser, B.

AU - van der Giet, M.

AU - Tate, R.

AU - Reinhard, J.

AU - Faissner, A.

AU - Joachim, S. C.

AU - Kociok, N.

N1 - This is a post-peer-review, pre-copyedit version of an article published in Pathology oncology research. The final authenticated version is available online at: https://doi.org/10.1007/s12253-017-0360-x

PY - 2017/11/15

Y1 - 2017/11/15

N2 - 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.

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KW - sphingosine-1-phosphate

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