TY  - JOUR
A1  - Kakkassery, Vinodh
A1  - Skosyrski, S.
A1  - Lüth, A.
A1  - Kleuser, Burkhard
A1  - van der Giet, Maria
A1  - Tate, R.
A1  - Reinhard, J.
A1  - Faissner, Andreas
A1  - Joachim, Stephanie Christine
A1  - Kociok, N.
T1  - Etoposide Upregulates Survival Favoring Sphingosine-1-Phosphate in Etoposide-Resistant Retinoblastoma Cells
JF  - Pathology & Oncology Research
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.
KW  - Retinoblastoma
KW  - Sphingosine-1-phosphate
KW  - Chemotherapy resistance
Y1  - 2017
U6  - https://doi.org/10.1007/s12253-017-0360-x
SN  - 1219-4956
SN  - 1532-2807
VL  - 25
IS  - 1
SP  - 391
EP  - 399
PB  - Springer
CY  - Dordrecht
ER  -