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N6-Isopentenyladenosine Hinders the Vasculogenic Mimicry in Human Glioblastoma Cells through Src-120 Catenin Pathway Modulation and RhoA Activity Inhibition
Background: Vasculogenic mimicry (VM) is a functional microcirculation pattern formed by aggressive tumor cells. Thus far, no effective drugs have been developed to target VM. Glioblastoma (GBM) is the most malignant form of brain cancer and is a highly vascularized tumor. Vasculogenic mimicry repre...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508824/ https://www.ncbi.nlm.nih.gov/pubmed/34638872 http://dx.doi.org/10.3390/ijms221910530 |
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author | Pagano, Cristina Navarra, Giovanna Pastorino, Olga Avilia, Giorgio Coppola, Laura Della Monica, Rosa Chiariotti, Lorenzo Florio, Tullio Corsaro, Alessandro Torelli, Giovanni Caiazzo, Pasquale Gazzerro, Patrizia Bifulco, Maurizio Laezza, Chiara |
author_facet | Pagano, Cristina Navarra, Giovanna Pastorino, Olga Avilia, Giorgio Coppola, Laura Della Monica, Rosa Chiariotti, Lorenzo Florio, Tullio Corsaro, Alessandro Torelli, Giovanni Caiazzo, Pasquale Gazzerro, Patrizia Bifulco, Maurizio Laezza, Chiara |
author_sort | Pagano, Cristina |
collection | PubMed |
description | Background: Vasculogenic mimicry (VM) is a functional microcirculation pattern formed by aggressive tumor cells. Thus far, no effective drugs have been developed to target VM. Glioblastoma (GBM) is the most malignant form of brain cancer and is a highly vascularized tumor. Vasculogenic mimicry represents a means whereby GBM can escape anti-angiogenic therapies. Methods: Here, using an in vitro tube formation assay on Matrigel, we evaluated the ability of N6-isopentenyladenosine (iPA) to interfere with vasculogenic mimicry (VM). RhoA activity was assessed using a pull-down assay, while the modulation of the adherens junctions proteins was analyzed by Western blot analysis. Results: We found that iPA at sublethal doses inhibited the formation of capillary-like structures suppressing cell migration and invasion of U87MG, U343MG, and U251MG cells, of patient-derived human GBM cells and GBM stem cells. iPA reduces the vascular endothelial cadherin (VE-cadherin) expression levels in a dose-dependent manner, impairs the vasculogenic mimicry network by modulation of the Src/p120-catenin pathway and inhibition of RhoA-GTPase activity. Conclusions: Taken together, our results revealed iPA as a promising novel anti-VM drug in GBM clinical therapeutics. |
format | Online Article Text |
id | pubmed-8508824 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85088242021-10-13 N6-Isopentenyladenosine Hinders the Vasculogenic Mimicry in Human Glioblastoma Cells through Src-120 Catenin Pathway Modulation and RhoA Activity Inhibition Pagano, Cristina Navarra, Giovanna Pastorino, Olga Avilia, Giorgio Coppola, Laura Della Monica, Rosa Chiariotti, Lorenzo Florio, Tullio Corsaro, Alessandro Torelli, Giovanni Caiazzo, Pasquale Gazzerro, Patrizia Bifulco, Maurizio Laezza, Chiara Int J Mol Sci Article Background: Vasculogenic mimicry (VM) is a functional microcirculation pattern formed by aggressive tumor cells. Thus far, no effective drugs have been developed to target VM. Glioblastoma (GBM) is the most malignant form of brain cancer and is a highly vascularized tumor. Vasculogenic mimicry represents a means whereby GBM can escape anti-angiogenic therapies. Methods: Here, using an in vitro tube formation assay on Matrigel, we evaluated the ability of N6-isopentenyladenosine (iPA) to interfere with vasculogenic mimicry (VM). RhoA activity was assessed using a pull-down assay, while the modulation of the adherens junctions proteins was analyzed by Western blot analysis. Results: We found that iPA at sublethal doses inhibited the formation of capillary-like structures suppressing cell migration and invasion of U87MG, U343MG, and U251MG cells, of patient-derived human GBM cells and GBM stem cells. iPA reduces the vascular endothelial cadherin (VE-cadherin) expression levels in a dose-dependent manner, impairs the vasculogenic mimicry network by modulation of the Src/p120-catenin pathway and inhibition of RhoA-GTPase activity. Conclusions: Taken together, our results revealed iPA as a promising novel anti-VM drug in GBM clinical therapeutics. MDPI 2021-09-29 /pmc/articles/PMC8508824/ /pubmed/34638872 http://dx.doi.org/10.3390/ijms221910530 Text en © 2021 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 Pagano, Cristina Navarra, Giovanna Pastorino, Olga Avilia, Giorgio Coppola, Laura Della Monica, Rosa Chiariotti, Lorenzo Florio, Tullio Corsaro, Alessandro Torelli, Giovanni Caiazzo, Pasquale Gazzerro, Patrizia Bifulco, Maurizio Laezza, Chiara N6-Isopentenyladenosine Hinders the Vasculogenic Mimicry in Human Glioblastoma Cells through Src-120 Catenin Pathway Modulation and RhoA Activity Inhibition |
title | N6-Isopentenyladenosine Hinders the Vasculogenic Mimicry in Human Glioblastoma Cells through Src-120 Catenin Pathway Modulation and RhoA Activity Inhibition |
title_full | N6-Isopentenyladenosine Hinders the Vasculogenic Mimicry in Human Glioblastoma Cells through Src-120 Catenin Pathway Modulation and RhoA Activity Inhibition |
title_fullStr | N6-Isopentenyladenosine Hinders the Vasculogenic Mimicry in Human Glioblastoma Cells through Src-120 Catenin Pathway Modulation and RhoA Activity Inhibition |
title_full_unstemmed | N6-Isopentenyladenosine Hinders the Vasculogenic Mimicry in Human Glioblastoma Cells through Src-120 Catenin Pathway Modulation and RhoA Activity Inhibition |
title_short | N6-Isopentenyladenosine Hinders the Vasculogenic Mimicry in Human Glioblastoma Cells through Src-120 Catenin Pathway Modulation and RhoA Activity Inhibition |
title_sort | n6-isopentenyladenosine hinders the vasculogenic mimicry in human glioblastoma cells through src-120 catenin pathway modulation and rhoa activity inhibition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508824/ https://www.ncbi.nlm.nih.gov/pubmed/34638872 http://dx.doi.org/10.3390/ijms221910530 |
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