The chaperone system in glioblastoma multiforme and derived cell lines: diagnostic and mechanistic implications

Background: Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Novel treatments are needed to counteract the molecular mechanisms of GBM growth and drug resistance. The chaperone system (CS) members are typically cytoprotective but some, termed Hsp, can bec...

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Main Authors: Giusi Alberti, Claudia Campanella, Letizia Paladino, Rossana Porcasi, Celeste Caruso Bavisotto, Alessandro Pitruzzella, Francesca Graziano, Ada Maria Florena, Antonina Argo, Everly Conway de Macario, Alberto JL Macario, Francesco Cappello, Fabio Bucchieri, Rosario Barone, Francesca Rappa
Format: Article
Language:English
Published: IMR Press 2022-03-01
Series:Frontiers in Bioscience-Landmark
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Online Access:https://www.imrpress.com/journal/FBL/27/3/10.31083/j.fbl2703097
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author Giusi Alberti
Claudia Campanella
Letizia Paladino
Rossana Porcasi
Celeste Caruso Bavisotto
Alessandro Pitruzzella
Francesca Graziano
Ada Maria Florena
Antonina Argo
Everly Conway de Macario
Alberto JL Macario
Francesco Cappello
Fabio Bucchieri
Rosario Barone
Francesca Rappa
author_facet Giusi Alberti
Claudia Campanella
Letizia Paladino
Rossana Porcasi
Celeste Caruso Bavisotto
Alessandro Pitruzzella
Francesca Graziano
Ada Maria Florena
Antonina Argo
Everly Conway de Macario
Alberto JL Macario
Francesco Cappello
Fabio Bucchieri
Rosario Barone
Francesca Rappa
author_sort Giusi Alberti
collection DOAJ
description Background: Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Novel treatments are needed to counteract the molecular mechanisms of GBM growth and drug resistance. The chaperone system (CS) members are typically cytoprotective but some, termed Hsp, can become pathogenic and participate in carcinogenesis, along with the vascular endothelial growth factor (VEGF), and we investigated them in GBM biopsies and derived cell lines. The objectives were to identify diagnostic-prognostic biomarkers and gather information for developing chaperonotherapy. Methods: Cell lines from GBMs were established, characterized (morphology, growth characteristics, and specific markers), and stored. Chaperones and angiogenic factors [Hsp10, Hsp27, Hsp60, Hsp70, Hsp90, FLT-1 (VEGFR-1), FLK1 (KDR, VEGFR-2), and FLT-4 (VEGFR-3)] were observed in cells by immunofluorescence while the chaperones were measured in tumor tissue by immunohistochemistry. Results: Four cell lines were derived from four different GBMs; the cells were spindle shaped or polygonal and grew at high rates as adherent monolayers or clusters without evidence of contact inhibition. The astrocyte-specific glial fibrillary acidic protein (GFAP); and the neuronal NSE, malignancy VIM, and proliferation PCNA, markers were determined. The cells expressed GFAP but no NSE, indicating that they were primary glioblastoma cell lines, with high levels of Hsp10, Hsp27, Hsp60, Hsp90, and Flk1; and low levels of Hsp70, Flt1, and Flt4. Conclusions: Four cell lines were established derived from four out of ten GBM tumors studied. The cell lines showed intense positivity for chaperones studied and factors connected to malignancy and the tumors showed increased levels of chaperones, making them potential diagnostic-prognostic biomarkers and targets for anti-cancer compounds.
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spelling doaj.art-735df559795d4cc7a83057e1176efb3c2022-12-21T19:06:39ZengIMR PressFrontiers in Bioscience-Landmark2768-67012022-03-0127309710.31083/j.fbl2703097S2768-6701(22)00435-XThe chaperone system in glioblastoma multiforme and derived cell lines: diagnostic and mechanistic implicationsGiusi Alberti0Claudia Campanella1Letizia Paladino2Rossana Porcasi3Celeste Caruso Bavisotto4Alessandro Pitruzzella5Francesca Graziano6Ada Maria Florena7Antonina Argo8Everly Conway de Macario9Alberto JL Macario10Francesco Cappello11Fabio Bucchieri12Rosario Barone13Francesca Rappa14Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, ItalyDepartment of Sciences for the Promotion of Health and Mother and Child Care, Anatomic Pathology, University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, ItalyDepartment of Neurosurgery, Highly Specialized Hospital and of National Importance “Garibaldi", 95122 Catania, ItalyDepartment of Sciences for the Promotion of Health and Mother and Child Care, Anatomic Pathology, University of Palermo, 90127 Palermo, ItalyDepartment of Health Promotion, Mother and Child Care, Section of Legal Medicine, University of Palermo, 90127 Palermo, ItalyDepartment of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore-Institute of Marine and Environmental Technology (IMET), Baltimore, MD 21202, USAEuro-Mediterranean Institutes of Science and Technology (IEMEST), 90139 Palermo, ItalyDepartment of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, ItalyDepartment of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, ItalyBackground: Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Novel treatments are needed to counteract the molecular mechanisms of GBM growth and drug resistance. The chaperone system (CS) members are typically cytoprotective but some, termed Hsp, can become pathogenic and participate in carcinogenesis, along with the vascular endothelial growth factor (VEGF), and we investigated them in GBM biopsies and derived cell lines. The objectives were to identify diagnostic-prognostic biomarkers and gather information for developing chaperonotherapy. Methods: Cell lines from GBMs were established, characterized (morphology, growth characteristics, and specific markers), and stored. Chaperones and angiogenic factors [Hsp10, Hsp27, Hsp60, Hsp70, Hsp90, FLT-1 (VEGFR-1), FLK1 (KDR, VEGFR-2), and FLT-4 (VEGFR-3)] were observed in cells by immunofluorescence while the chaperones were measured in tumor tissue by immunohistochemistry. Results: Four cell lines were derived from four different GBMs; the cells were spindle shaped or polygonal and grew at high rates as adherent monolayers or clusters without evidence of contact inhibition. The astrocyte-specific glial fibrillary acidic protein (GFAP); and the neuronal NSE, malignancy VIM, and proliferation PCNA, markers were determined. The cells expressed GFAP but no NSE, indicating that they were primary glioblastoma cell lines, with high levels of Hsp10, Hsp27, Hsp60, Hsp90, and Flk1; and low levels of Hsp70, Flt1, and Flt4. Conclusions: Four cell lines were established derived from four out of ten GBM tumors studied. The cell lines showed intense positivity for chaperones studied and factors connected to malignancy and the tumors showed increased levels of chaperones, making them potential diagnostic-prognostic biomarkers and targets for anti-cancer compounds.https://www.imrpress.com/journal/FBL/27/3/10.31083/j.fbl2703097glioblastoma multiforme (gbm)chaperone system (cs)heat shock protein (hsp)vascular endothelial growth factor (vegf)gmb cell lines
spellingShingle Giusi Alberti
Claudia Campanella
Letizia Paladino
Rossana Porcasi
Celeste Caruso Bavisotto
Alessandro Pitruzzella
Francesca Graziano
Ada Maria Florena
Antonina Argo
Everly Conway de Macario
Alberto JL Macario
Francesco Cappello
Fabio Bucchieri
Rosario Barone
Francesca Rappa
The chaperone system in glioblastoma multiforme and derived cell lines: diagnostic and mechanistic implications
Frontiers in Bioscience-Landmark
glioblastoma multiforme (gbm)
chaperone system (cs)
heat shock protein (hsp)
vascular endothelial growth factor (vegf)
gmb cell lines
title The chaperone system in glioblastoma multiforme and derived cell lines: diagnostic and mechanistic implications
title_full The chaperone system in glioblastoma multiforme and derived cell lines: diagnostic and mechanistic implications
title_fullStr The chaperone system in glioblastoma multiforme and derived cell lines: diagnostic and mechanistic implications
title_full_unstemmed The chaperone system in glioblastoma multiforme and derived cell lines: diagnostic and mechanistic implications
title_short The chaperone system in glioblastoma multiforme and derived cell lines: diagnostic and mechanistic implications
title_sort chaperone system in glioblastoma multiforme and derived cell lines diagnostic and mechanistic implications
topic glioblastoma multiforme (gbm)
chaperone system (cs)
heat shock protein (hsp)
vascular endothelial growth factor (vegf)
gmb cell lines
url https://www.imrpress.com/journal/FBL/27/3/10.31083/j.fbl2703097
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