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...
Main Authors: | , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
IMR Press
2022-03-01
|
Series: | Frontiers in Bioscience-Landmark |
Subjects: | |
Online Access: | https://www.imrpress.com/journal/FBL/27/3/10.31083/j.fbl2703097 |
_version_ | 1819046844059090944 |
---|---|
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. |
first_indexed | 2024-12-21T10:50:55Z |
format | Article |
id | doaj.art-735df559795d4cc7a83057e1176efb3c |
institution | Directory Open Access Journal |
issn | 2768-6701 |
language | English |
last_indexed | 2024-12-21T10:50:55Z |
publishDate | 2022-03-01 |
publisher | IMR Press |
record_format | Article |
series | Frontiers in Bioscience-Landmark |
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 |
work_keys_str_mv | AT giusialberti thechaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT claudiacampanella thechaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT letiziapaladino thechaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT rossanaporcasi thechaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT celestecarusobavisotto thechaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT alessandropitruzzella thechaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT francescagraziano thechaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT adamariaflorena thechaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT antoninaargo thechaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT everlyconwaydemacario thechaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT albertojlmacario thechaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT francescocappello thechaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT fabiobucchieri thechaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT rosariobarone thechaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT francescarappa thechaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT giusialberti chaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT claudiacampanella chaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT letiziapaladino chaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT rossanaporcasi chaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT celestecarusobavisotto chaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT alessandropitruzzella chaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT francescagraziano chaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT adamariaflorena chaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT antoninaargo chaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT everlyconwaydemacario chaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT albertojlmacario chaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT francescocappello chaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT fabiobucchieri chaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT rosariobarone chaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications AT francescarappa chaperonesysteminglioblastomamultiformeandderivedcelllinesdiagnosticandmechanisticimplications |