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Glypican-1 in human glioblastoma: implications in tumorigenesis and chemotherapy

Glioblastoma is one of the most common malignant brain tumors, with which patients have a mean survival of 24 months. Glypican-1 has been previously shown to be overexpressed in human glioblastoma and to be negatively correlated with patient’s survival. This study aimed to investigate how glypican-1...

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Autores principales: Listik, Eduardo, Toma, Leny
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061737/
https://www.ncbi.nlm.nih.gov/pubmed/32180897
http://dx.doi.org/10.18632/oncotarget.27492
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author Listik, Eduardo
Toma, Leny
author_facet Listik, Eduardo
Toma, Leny
author_sort Listik, Eduardo
collection PubMed
description Glioblastoma is one of the most common malignant brain tumors, with which patients have a mean survival of 24 months. Glypican-1 has been previously shown to be overexpressed in human glioblastoma and to be negatively correlated with patient’s survival. This study aimed to investigate how glypican-1 influences the tumoral profile of human glioblastoma using in vitro cell line models. By downregulating the expression of glypican-1 in U-251 MG cells, we observed that the cellular growth and proliferation were highly reduced, in which cells were significantly shifted towards G0 as opposed to G1 phases. Cellular migration was severely affected, and glypican-1 majorly impacted the affinity towards laminin-binding of glioblastoma U-251 MG cells. This proteoglycan was highly prevalent in glioblastoma cells, being primarily localized in the cellular membrane and extracellular vesicles, occasionally with glypican-3. Glypican-1 could also be found in cell-cell junctions with syndecan-4 but was not identified in lipid rafts in this study. Glypican-1-silenced cells were much more susceptible to temozolomide than in U-251 MG itself. Therefore, we present evidence not only to support facts that glypican-1 is an elementary macromolecule in glioblastoma tumoral microenvironment but also to introduce this proteoglycan as a promising therapeutic target for this lethal tumor.
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spelling pubmed-70617372020-03-16 Glypican-1 in human glioblastoma: implications in tumorigenesis and chemotherapy Listik, Eduardo Toma, Leny Oncotarget Research Paper Glioblastoma is one of the most common malignant brain tumors, with which patients have a mean survival of 24 months. Glypican-1 has been previously shown to be overexpressed in human glioblastoma and to be negatively correlated with patient’s survival. This study aimed to investigate how glypican-1 influences the tumoral profile of human glioblastoma using in vitro cell line models. By downregulating the expression of glypican-1 in U-251 MG cells, we observed that the cellular growth and proliferation were highly reduced, in which cells were significantly shifted towards G0 as opposed to G1 phases. Cellular migration was severely affected, and glypican-1 majorly impacted the affinity towards laminin-binding of glioblastoma U-251 MG cells. This proteoglycan was highly prevalent in glioblastoma cells, being primarily localized in the cellular membrane and extracellular vesicles, occasionally with glypican-3. Glypican-1 could also be found in cell-cell junctions with syndecan-4 but was not identified in lipid rafts in this study. Glypican-1-silenced cells were much more susceptible to temozolomide than in U-251 MG itself. Therefore, we present evidence not only to support facts that glypican-1 is an elementary macromolecule in glioblastoma tumoral microenvironment but also to introduce this proteoglycan as a promising therapeutic target for this lethal tumor. Impact Journals LLC 2020-03-03 /pmc/articles/PMC7061737/ /pubmed/32180897 http://dx.doi.org/10.18632/oncotarget.27492 Text en http://creativecommons.org/licenses/by/3.0/ Copyright: Listik and Toma. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Listik, Eduardo
Toma, Leny
Glypican-1 in human glioblastoma: implications in tumorigenesis and chemotherapy
title Glypican-1 in human glioblastoma: implications in tumorigenesis and chemotherapy
title_full Glypican-1 in human glioblastoma: implications in tumorigenesis and chemotherapy
title_fullStr Glypican-1 in human glioblastoma: implications in tumorigenesis and chemotherapy
title_full_unstemmed Glypican-1 in human glioblastoma: implications in tumorigenesis and chemotherapy
title_short Glypican-1 in human glioblastoma: implications in tumorigenesis and chemotherapy
title_sort glypican-1 in human glioblastoma: implications in tumorigenesis and chemotherapy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061737/
https://www.ncbi.nlm.nih.gov/pubmed/32180897
http://dx.doi.org/10.18632/oncotarget.27492
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