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

doi:10.1007/s12253-017-0360-x

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

^*Korrespondierende/r Autor/-in für diese Arbeit

Klinik für Augenheilkunde

6 Zitate (Scopus)

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 0.2). 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.

Originalsprache	Englisch
Zeitschrift	Pathology and Oncology Research
Jahrgang	25
Ausgabenummer	1
Seiten (von - bis)	391-399
Seitenumfang	9
ISSN	1219-4956
DOIs	https://doi.org/10.1007/s12253-017-0360-x
Publikationsstatus	Veröffentlicht - 15.01.2019

Fördermittel

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

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Profilbereich: Lübeck Integrated Oncology Network (LION)

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10.1007/s12253-017-0360-x

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title = "Etoposide Upregulates Survival Favoring Sphingosine-1-Phosphate in Etoposide-Resistant Retinoblastoma Cells",

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 0.2). 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.",

author = "Vinodh Kakkassery and S. Skosyrski and A. L{\"u}th and B. Kleuser and \{van der Giet\}, M. and R. Tate and J. Reinhard and A. Faissner and Joachim, \{S. C.\} and N. Kociok",

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doi = "10.1007/s12253-017-0360-x",

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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.

PY - 2019/1/15

Y1 - 2019/1/15

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 0.2). 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.

AB - 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 0.2). 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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Etoposide Upregulates Survival Favoring Sphingosine-1-Phosphate in Etoposide-Resistant Retinoblastoma Cells

Abstract

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