Cargando…
Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme
A signaling molecule which is involved in proliferation and migration of malignant cells is the lipid mediator sphingosine-1-phosphate (S1P). There are hints for a potential role of S1P signaling in malignant brain tumors such as glioblastoma multiforme (GBM) which is characterized by a poor prognos...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914339/ https://www.ncbi.nlm.nih.gov/pubmed/26887055 http://dx.doi.org/10.18632/oncotarget.7366 |
_version_ | 1782438546995412992 |
---|---|
author | Bien-Möller, Sandra Lange, Sandra Holm, Tobias Böhm, Andreas Paland, Heiko Küpper, Johannes Herzog, Susann Weitmann, Kerstin Havemann, Christoph Vogelgesang, Silke Marx, Sascha Hoffmann, Wolfgang Schroeder, Henry W.S. Rauch, Bernhard H. |
author_facet | Bien-Möller, Sandra Lange, Sandra Holm, Tobias Böhm, Andreas Paland, Heiko Küpper, Johannes Herzog, Susann Weitmann, Kerstin Havemann, Christoph Vogelgesang, Silke Marx, Sascha Hoffmann, Wolfgang Schroeder, Henry W.S. Rauch, Bernhard H. |
author_sort | Bien-Möller, Sandra |
collection | PubMed |
description | A signaling molecule which is involved in proliferation and migration of malignant cells is the lipid mediator sphingosine-1-phosphate (S1P). There are hints for a potential role of S1P signaling in malignant brain tumors such as glioblastoma multiforme (GBM) which is characterized by a poor prognosis. Therefore, a comprehensive expression analysis of S1P receptors (S1P(1)-S1P(5)) and S1P metabolizing enzymes in human GBM (n = 117) compared to healthy brain (n = 10) was performed to evaluate their role for patient's survival. Furthermore, influence of S1P receptor inhibition on proliferation and migration were studied in LN18 GBM cells. Compared to control brain, mRNA levels of S1P(1), S1P(2), S1P(3) and S1P generating sphingosine kinase-1 were elevated in GBM. Kaplan-Meier analyses demonstrated an association between S1P(1) and S1P(2) with patient's survival times. In vitro, an inhibitory effect of the SphK inhibitor SKI-II on viability of LN18 cells was shown. S1P itself had no effect on viability but stimulated LN18 migration which was blocked by inhibition of S1P(1) and S1P(2). The participation of S1P(1) and S1P(2) in LN18 migration was further supported by siRNA-mediated silencing of these receptors. Immunoblots and inhibition experiments suggest an involvement of the PI3-kinase/AKT1 pathway in the chemotactic effect of S1P in LN18 cells. In summary, our data argue for a role of S1P signaling in proliferation and migration of GBM cells. Individual components of the S1P pathway represent prognostic factors for patients with GBM. Perspectively, a selective modulation of S1P receptor subtypes could represent a therapeutic approach for GBM patients and requires further evaluation. |
format | Online Article Text |
id | pubmed-4914339 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-49143392016-07-11 Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme Bien-Möller, Sandra Lange, Sandra Holm, Tobias Böhm, Andreas Paland, Heiko Küpper, Johannes Herzog, Susann Weitmann, Kerstin Havemann, Christoph Vogelgesang, Silke Marx, Sascha Hoffmann, Wolfgang Schroeder, Henry W.S. Rauch, Bernhard H. Oncotarget Research Paper A signaling molecule which is involved in proliferation and migration of malignant cells is the lipid mediator sphingosine-1-phosphate (S1P). There are hints for a potential role of S1P signaling in malignant brain tumors such as glioblastoma multiforme (GBM) which is characterized by a poor prognosis. Therefore, a comprehensive expression analysis of S1P receptors (S1P(1)-S1P(5)) and S1P metabolizing enzymes in human GBM (n = 117) compared to healthy brain (n = 10) was performed to evaluate their role for patient's survival. Furthermore, influence of S1P receptor inhibition on proliferation and migration were studied in LN18 GBM cells. Compared to control brain, mRNA levels of S1P(1), S1P(2), S1P(3) and S1P generating sphingosine kinase-1 were elevated in GBM. Kaplan-Meier analyses demonstrated an association between S1P(1) and S1P(2) with patient's survival times. In vitro, an inhibitory effect of the SphK inhibitor SKI-II on viability of LN18 cells was shown. S1P itself had no effect on viability but stimulated LN18 migration which was blocked by inhibition of S1P(1) and S1P(2). The participation of S1P(1) and S1P(2) in LN18 migration was further supported by siRNA-mediated silencing of these receptors. Immunoblots and inhibition experiments suggest an involvement of the PI3-kinase/AKT1 pathway in the chemotactic effect of S1P in LN18 cells. In summary, our data argue for a role of S1P signaling in proliferation and migration of GBM cells. Individual components of the S1P pathway represent prognostic factors for patients with GBM. Perspectively, a selective modulation of S1P receptor subtypes could represent a therapeutic approach for GBM patients and requires further evaluation. Impact Journals LLC 2016-02-13 /pmc/articles/PMC4914339/ /pubmed/26887055 http://dx.doi.org/10.18632/oncotarget.7366 Text en Copyright: © 2016 Bien-Möller et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Bien-Möller, Sandra Lange, Sandra Holm, Tobias Böhm, Andreas Paland, Heiko Küpper, Johannes Herzog, Susann Weitmann, Kerstin Havemann, Christoph Vogelgesang, Silke Marx, Sascha Hoffmann, Wolfgang Schroeder, Henry W.S. Rauch, Bernhard H. Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme |
title | Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme |
title_full | Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme |
title_fullStr | Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme |
title_full_unstemmed | Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme |
title_short | Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme |
title_sort | expression of s1p metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914339/ https://www.ncbi.nlm.nih.gov/pubmed/26887055 http://dx.doi.org/10.18632/oncotarget.7366 |
work_keys_str_mv | AT bienmollersandra expressionofs1pmetabolizingenzymesandreceptorscorrelatewithsurvivaltimeandregulatecellmigrationinglioblastomamultiforme AT langesandra expressionofs1pmetabolizingenzymesandreceptorscorrelatewithsurvivaltimeandregulatecellmigrationinglioblastomamultiforme AT holmtobias expressionofs1pmetabolizingenzymesandreceptorscorrelatewithsurvivaltimeandregulatecellmigrationinglioblastomamultiforme AT bohmandreas expressionofs1pmetabolizingenzymesandreceptorscorrelatewithsurvivaltimeandregulatecellmigrationinglioblastomamultiforme AT palandheiko expressionofs1pmetabolizingenzymesandreceptorscorrelatewithsurvivaltimeandregulatecellmigrationinglioblastomamultiforme AT kupperjohannes expressionofs1pmetabolizingenzymesandreceptorscorrelatewithsurvivaltimeandregulatecellmigrationinglioblastomamultiforme AT herzogsusann expressionofs1pmetabolizingenzymesandreceptorscorrelatewithsurvivaltimeandregulatecellmigrationinglioblastomamultiforme AT weitmannkerstin expressionofs1pmetabolizingenzymesandreceptorscorrelatewithsurvivaltimeandregulatecellmigrationinglioblastomamultiforme AT havemannchristoph expressionofs1pmetabolizingenzymesandreceptorscorrelatewithsurvivaltimeandregulatecellmigrationinglioblastomamultiforme AT vogelgesangsilke expressionofs1pmetabolizingenzymesandreceptorscorrelatewithsurvivaltimeandregulatecellmigrationinglioblastomamultiforme AT marxsascha expressionofs1pmetabolizingenzymesandreceptorscorrelatewithsurvivaltimeandregulatecellmigrationinglioblastomamultiforme AT hoffmannwolfgang expressionofs1pmetabolizingenzymesandreceptorscorrelatewithsurvivaltimeandregulatecellmigrationinglioblastomamultiforme AT schroederhenryws expressionofs1pmetabolizingenzymesandreceptorscorrelatewithsurvivaltimeandregulatecellmigrationinglioblastomamultiforme AT rauchbernhardh expressionofs1pmetabolizingenzymesandreceptorscorrelatewithsurvivaltimeandregulatecellmigrationinglioblastomamultiforme |