Cargando…

Glucose and Inositol Transporters, SLC5A1 and SLC5A3, in Glioblastoma Cell Migration

SIMPLE SUMMARY: Cell migration is the main obstacle to the treatment of highly invasive brain cancer glioblastoma multiforme (GBM). We investigated in vitro the potential role of two solute carrier proteins (SLCs), SLC5A1 and SLC5A3, and their respective substrates, glucose and inositol, in GBM cell...

Descripción completa

Detalles Bibliográficos
Autores principales: Brosch, Philippa K., Korsa, Tessa, Taban, Danush, Eiring, Patrick, Hildebrand, Sascha, Neubauer, Julia, Zimmermann, Heiko, Sauer, Markus, Shirakashi, Ryo, Djuzenova, Cholpon S., Sisario, Dmitri, Sukhorukov, Vladimir L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738886/
https://www.ncbi.nlm.nih.gov/pubmed/36497276
http://dx.doi.org/10.3390/cancers14235794
_version_ 1784847661362315264
author Brosch, Philippa K.
Korsa, Tessa
Taban, Danush
Eiring, Patrick
Hildebrand, Sascha
Neubauer, Julia
Zimmermann, Heiko
Sauer, Markus
Shirakashi, Ryo
Djuzenova, Cholpon S.
Sisario, Dmitri
Sukhorukov, Vladimir L.
author_facet Brosch, Philippa K.
Korsa, Tessa
Taban, Danush
Eiring, Patrick
Hildebrand, Sascha
Neubauer, Julia
Zimmermann, Heiko
Sauer, Markus
Shirakashi, Ryo
Djuzenova, Cholpon S.
Sisario, Dmitri
Sukhorukov, Vladimir L.
author_sort Brosch, Philippa K.
collection PubMed
description SIMPLE SUMMARY: Cell migration is the main obstacle to the treatment of highly invasive brain cancer glioblastoma multiforme (GBM). We investigated in vitro the potential role of two solute carrier proteins (SLCs), SLC5A1 and SLC5A3, and their respective substrates, glucose and inositol, in GBM cell migration. We found that GBM cell motility was increased by medium supplementation with glucose and inositol and was strongly impaired by inhibition of SLC5A1/3 proteins. Using conventional and super-resolution fluorescence microscopy, we showed that both SLCs were not only highly expressed in migrating GBM cells, but they also localized to the lamellipodia, i.e., the migration-governing cell protrusions. Taken together, our data suggest that SLC5A1 and SLC5A3 are involved in GBM cell migration, presumably by mediating solute transport, osmotic water fluxes and thus local volume regulation in the lamellipodium. ABSTRACT: (1) Background: The recurrence of glioblastoma multiforme (GBM) is mainly due to invasion of the surrounding brain tissue, where organic solutes, including glucose and inositol, are abundant. Invasive cell migration has been linked to the aberrant expression of transmembrane solute-linked carriers (SLC). Here, we explore the role of glucose (SLC5A1) and inositol transporters (SLC5A3) in GBM cell migration. (2) Methods: Using immunofluorescence microscopy, we visualized the subcellular localization of SLC5A1 and SLC5A3 in two highly motile human GBM cell lines. We also employed wound-healing assays to examine the effect of SLC inhibition on GBM cell migration and examined the chemotactic potential of inositol. (3) Results: While GBM cell migration was significantly increased by extracellular inositol and glucose, it was strongly impaired by SLC transporter inhibition. In the GBM cell monolayers, both SLCs were exclusively detected in the migrating cells at the monolayer edge. In single GBM cells, both transporters were primarily localized at the leading edge of the lamellipodium. Interestingly, in GBM cells migrating via blebbing, SLC5A1 and SLC5A3 were predominantly detected in nascent and mature blebs, respectively. (4) Conclusion: We provide several lines of evidence for the involvement of SLC5A1 and SLC5A3 in GBM cell migration, thereby complementing the migration-associated transportome. Our findings suggest that SLC inhibition is a promising approach to GBM treatment.
format Online
Article
Text
id pubmed-9738886
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-97388862022-12-11 Glucose and Inositol Transporters, SLC5A1 and SLC5A3, in Glioblastoma Cell Migration Brosch, Philippa K. Korsa, Tessa Taban, Danush Eiring, Patrick Hildebrand, Sascha Neubauer, Julia Zimmermann, Heiko Sauer, Markus Shirakashi, Ryo Djuzenova, Cholpon S. Sisario, Dmitri Sukhorukov, Vladimir L. Cancers (Basel) Article SIMPLE SUMMARY: Cell migration is the main obstacle to the treatment of highly invasive brain cancer glioblastoma multiforme (GBM). We investigated in vitro the potential role of two solute carrier proteins (SLCs), SLC5A1 and SLC5A3, and their respective substrates, glucose and inositol, in GBM cell migration. We found that GBM cell motility was increased by medium supplementation with glucose and inositol and was strongly impaired by inhibition of SLC5A1/3 proteins. Using conventional and super-resolution fluorescence microscopy, we showed that both SLCs were not only highly expressed in migrating GBM cells, but they also localized to the lamellipodia, i.e., the migration-governing cell protrusions. Taken together, our data suggest that SLC5A1 and SLC5A3 are involved in GBM cell migration, presumably by mediating solute transport, osmotic water fluxes and thus local volume regulation in the lamellipodium. ABSTRACT: (1) Background: The recurrence of glioblastoma multiforme (GBM) is mainly due to invasion of the surrounding brain tissue, where organic solutes, including glucose and inositol, are abundant. Invasive cell migration has been linked to the aberrant expression of transmembrane solute-linked carriers (SLC). Here, we explore the role of glucose (SLC5A1) and inositol transporters (SLC5A3) in GBM cell migration. (2) Methods: Using immunofluorescence microscopy, we visualized the subcellular localization of SLC5A1 and SLC5A3 in two highly motile human GBM cell lines. We also employed wound-healing assays to examine the effect of SLC inhibition on GBM cell migration and examined the chemotactic potential of inositol. (3) Results: While GBM cell migration was significantly increased by extracellular inositol and glucose, it was strongly impaired by SLC transporter inhibition. In the GBM cell monolayers, both SLCs were exclusively detected in the migrating cells at the monolayer edge. In single GBM cells, both transporters were primarily localized at the leading edge of the lamellipodium. Interestingly, in GBM cells migrating via blebbing, SLC5A1 and SLC5A3 were predominantly detected in nascent and mature blebs, respectively. (4) Conclusion: We provide several lines of evidence for the involvement of SLC5A1 and SLC5A3 in GBM cell migration, thereby complementing the migration-associated transportome. Our findings suggest that SLC inhibition is a promising approach to GBM treatment. MDPI 2022-11-24 /pmc/articles/PMC9738886/ /pubmed/36497276 http://dx.doi.org/10.3390/cancers14235794 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Brosch, Philippa K.
Korsa, Tessa
Taban, Danush
Eiring, Patrick
Hildebrand, Sascha
Neubauer, Julia
Zimmermann, Heiko
Sauer, Markus
Shirakashi, Ryo
Djuzenova, Cholpon S.
Sisario, Dmitri
Sukhorukov, Vladimir L.
Glucose and Inositol Transporters, SLC5A1 and SLC5A3, in Glioblastoma Cell Migration
title Glucose and Inositol Transporters, SLC5A1 and SLC5A3, in Glioblastoma Cell Migration
title_full Glucose and Inositol Transporters, SLC5A1 and SLC5A3, in Glioblastoma Cell Migration
title_fullStr Glucose and Inositol Transporters, SLC5A1 and SLC5A3, in Glioblastoma Cell Migration
title_full_unstemmed Glucose and Inositol Transporters, SLC5A1 and SLC5A3, in Glioblastoma Cell Migration
title_short Glucose and Inositol Transporters, SLC5A1 and SLC5A3, in Glioblastoma Cell Migration
title_sort glucose and inositol transporters, slc5a1 and slc5a3, in glioblastoma cell migration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738886/
https://www.ncbi.nlm.nih.gov/pubmed/36497276
http://dx.doi.org/10.3390/cancers14235794
work_keys_str_mv AT broschphilippak glucoseandinositoltransportersslc5a1andslc5a3inglioblastomacellmigration
AT korsatessa glucoseandinositoltransportersslc5a1andslc5a3inglioblastomacellmigration
AT tabandanush glucoseandinositoltransportersslc5a1andslc5a3inglioblastomacellmigration
AT eiringpatrick glucoseandinositoltransportersslc5a1andslc5a3inglioblastomacellmigration
AT hildebrandsascha glucoseandinositoltransportersslc5a1andslc5a3inglioblastomacellmigration
AT neubauerjulia glucoseandinositoltransportersslc5a1andslc5a3inglioblastomacellmigration
AT zimmermannheiko glucoseandinositoltransportersslc5a1andslc5a3inglioblastomacellmigration
AT sauermarkus glucoseandinositoltransportersslc5a1andslc5a3inglioblastomacellmigration
AT shirakashiryo glucoseandinositoltransportersslc5a1andslc5a3inglioblastomacellmigration
AT djuzenovacholpons glucoseandinositoltransportersslc5a1andslc5a3inglioblastomacellmigration
AT sisariodmitri glucoseandinositoltransportersslc5a1andslc5a3inglioblastomacellmigration
AT sukhorukovvladimirl glucoseandinositoltransportersslc5a1andslc5a3inglioblastomacellmigration