Diversified expression of NG2/CSPG4 isoforms in glioblastoma and human foetal brain identifies pericyte subsets
NG2/CSPG4 is a complex surface-associated proteoglycan (PG) recognized to be a widely expressed membrane component of glioblastoma (WHO grade IV) cells and angiogenic pericytes. To determine the precise expression pattern of NG2/CSPG4 on glioblastoma cells and pericytes, we generated a panel of >...
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| description | NG2/CSPG4 is a complex surface-associated proteoglycan (PG) recognized to be a widely expressed membrane component of glioblastoma (WHO grade IV) cells and angiogenic pericytes. To determine the precise expression pattern of NG2/CSPG4 on glioblastoma cells and pericytes, we generated a panel of >60 mouse monoclonal antibodies (mAbs) directed against the ectodomain of human NG2/CSPG4, partially characterized the mAbs, and performed a high-resolution distributional mapping of the PG in human foetal, adult and glioblastoma-affected brains. The reactivity pattern initially observed on reference tumour cell lines indicated that the mAbs recognized 48 immunologically distinct NG2/CSPG4 isoforms, and a total of 14 mAbs was found to identify NG2/CSPG4 isoforms in foetal and neoplastic cerebral sections. These were consistently absent in the adult brain, but exhibited a complementary expression pattern in angiogenic vessels of both tumour and foetal tissues. Considering the extreme pleomorphism of tumour areas, and with the aim of subsequently analysing the distributional pattern of the NG2/CSPG4 isoforms on similar histological vessel typologies, a preliminary study was carried out with endothelial cell and pericyte markers, and with selected vascular basement membrane (VBM) components. On both tumour areas characterized by 'glomeruloid' and 'garland vessels', which showed a remarkably similar cellular and molecular organization, and on developing brain vessels, spatially separated, phenotypically diversified pericyte subsets with a polarized expression of key surface components, including NG2/CSPG4, were disclosed. Interestingly, the majority of the immunolocalized NG2/CSPG4 isoforms present in glioblastoma tissue were present in foetal brain, except for one isoform that seemed to be exclusive of tumour cells, being absent in foetal brain. The results highlight an unprecedented, complex pattern of NG2/CSPG4 isoform expression in foetal and neoplastic CNS, discriminating between phenotype-specific and neoplastic versus non-neoplastic variants of the PG, thus opening up vistas for more selective immunotherapeutic targeting of brain tumours. |
| doi_str_mv | 10.1371/journal.pone.0084883 |
| format | Article |
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To determine the precise expression pattern of NG2/CSPG4 on glioblastoma cells and pericytes, we generated a panel of >60 mouse monoclonal antibodies (mAbs) directed against the ectodomain of human NG2/CSPG4, partially characterized the mAbs, and performed a high-resolution distributional mapping of the PG in human foetal, adult and glioblastoma-affected brains. The reactivity pattern initially observed on reference tumour cell lines indicated that the mAbs recognized 48 immunologically distinct NG2/CSPG4 isoforms, and a total of 14 mAbs was found to identify NG2/CSPG4 isoforms in foetal and neoplastic cerebral sections. These were consistently absent in the adult brain, but exhibited a complementary expression pattern in angiogenic vessels of both tumour and foetal tissues. Considering the extreme pleomorphism of tumour areas, and with the aim of subsequently analysing the distributional pattern of the NG2/CSPG4 isoforms on similar histological vessel typologies, a preliminary study was carried out with endothelial cell and pericyte markers, and with selected vascular basement membrane (VBM) components. On both tumour areas characterized by 'glomeruloid' and 'garland vessels', which showed a remarkably similar cellular and molecular organization, and on developing brain vessels, spatially separated, phenotypically diversified pericyte subsets with a polarized expression of key surface components, including NG2/CSPG4, were disclosed. Interestingly, the majority of the immunolocalized NG2/CSPG4 isoforms present in glioblastoma tissue were present in foetal brain, except for one isoform that seemed to be exclusive of tumour cells, being absent in foetal brain. The results highlight an unprecedented, complex pattern of NG2/CSPG4 isoform expression in foetal and neoplastic CNS, discriminating between phenotype-specific and neoplastic versus non-neoplastic variants of the PG, thus opening up vistas for more selective immunotherapeutic targeting of brain tumours.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0084883</identifier><identifier>PMID: 24386429</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Angiogenesis ; Animals ; Antibodies, Monoclonal, Murine-Derived - chemistry ; Antibodies, Neoplasm - chemistry ; Blood vessels ; Brain ; Brain - metabolism ; Brain - pathology ; Brain architecture ; Brain cancer ; Brain Neoplasms - metabolism ; Brain Neoplasms - pathology ; Brain tumors ; Cancer therapies ; Cell Line, Tumor ; Central nervous system ; Chondroitin Sulfate Proteoglycans - biosynthesis ; Endothelial cells ; Ethics ; Female ; Fetus - metabolism ; Fetus - pathology ; Gene Expression Regulation, Neoplastic ; Glioblastoma ; Glioblastoma - metabolism ; Glioblastoma - pathology ; Glioblastoma cells ; Glucose ; Humans ; Isoforms ; Male ; Medicine ; Membrane Proteins - biosynthesis ; Mice ; Mice, Inbred BALB C ; Monoclonal antibodies ; Neoplasm Proteins - biosynthesis ; Neurosciences ; Neurosurgery ; Oncology ; Pericytes ; Pericytes - metabolism ; Pericytes - pathology ; Pleomorphism ; Protein Isoforms - biosynthesis ; Rodents ; Stem cells ; Tissues ; Tumor cell lines ; Tumors</subject><ispartof>PloS one, 2013-12, Vol.8 (12), p.e84883-e84883</ispartof><rights>2013 Francesco Girolamo. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Considering the extreme pleomorphism of tumour areas, and with the aim of subsequently analysing the distributional pattern of the NG2/CSPG4 isoforms on similar histological vessel typologies, a preliminary study was carried out with endothelial cell and pericyte markers, and with selected vascular basement membrane (VBM) components. On both tumour areas characterized by 'glomeruloid' and 'garland vessels', which showed a remarkably similar cellular and molecular organization, and on developing brain vessels, spatially separated, phenotypically diversified pericyte subsets with a polarized expression of key surface components, including NG2/CSPG4, were disclosed. Interestingly, the majority of the immunolocalized NG2/CSPG4 isoforms present in glioblastoma tissue were present in foetal brain, except for one isoform that seemed to be exclusive of tumour cells, being absent in foetal brain. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Girolamo, Francesco</au><au>Dallatomasina, Alice</au><au>Rizzi, Marco</au><au>Errede, Mariella</au><au>Wälchli, Thomas</au><au>Mucignat, Maria Teresa</au><au>Frei, Karl</au><au>Roncali, Luisa</au><au>Perris, Roberto</au><au>Virgintino, Daniela</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diversified expression of NG2/CSPG4 isoforms in glioblastoma and human foetal brain identifies pericyte subsets</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-12-26</date><risdate>2013</risdate><volume>8</volume><issue>12</issue><spage>e84883</spage><epage>e84883</epage><pages>e84883-e84883</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>NG2/CSPG4 is a complex surface-associated proteoglycan (PG) recognized to be a widely expressed membrane component of glioblastoma (WHO grade IV) cells and angiogenic pericytes. To determine the precise expression pattern of NG2/CSPG4 on glioblastoma cells and pericytes, we generated a panel of >60 mouse monoclonal antibodies (mAbs) directed against the ectodomain of human NG2/CSPG4, partially characterized the mAbs, and performed a high-resolution distributional mapping of the PG in human foetal, adult and glioblastoma-affected brains. The reactivity pattern initially observed on reference tumour cell lines indicated that the mAbs recognized 48 immunologically distinct NG2/CSPG4 isoforms, and a total of 14 mAbs was found to identify NG2/CSPG4 isoforms in foetal and neoplastic cerebral sections. These were consistently absent in the adult brain, but exhibited a complementary expression pattern in angiogenic vessels of both tumour and foetal tissues. Considering the extreme pleomorphism of tumour areas, and with the aim of subsequently analysing the distributional pattern of the NG2/CSPG4 isoforms on similar histological vessel typologies, a preliminary study was carried out with endothelial cell and pericyte markers, and with selected vascular basement membrane (VBM) components. On both tumour areas characterized by 'glomeruloid' and 'garland vessels', which showed a remarkably similar cellular and molecular organization, and on developing brain vessels, spatially separated, phenotypically diversified pericyte subsets with a polarized expression of key surface components, including NG2/CSPG4, were disclosed. Interestingly, the majority of the immunolocalized NG2/CSPG4 isoforms present in glioblastoma tissue were present in foetal brain, except for one isoform that seemed to be exclusive of tumour cells, being absent in foetal brain. The results highlight an unprecedented, complex pattern of NG2/CSPG4 isoform expression in foetal and neoplastic CNS, discriminating between phenotype-specific and neoplastic versus non-neoplastic variants of the PG, thus opening up vistas for more selective immunotherapeutic targeting of brain tumours.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24386429</pmid><doi>10.1371/journal.pone.0084883</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-12, Vol.8 (12), p.e84883-e84883 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1470907758 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adult Angiogenesis Animals Antibodies, Monoclonal, Murine-Derived - chemistry Antibodies, Neoplasm - chemistry Blood vessels Brain Brain - metabolism Brain - pathology Brain architecture Brain cancer Brain Neoplasms - metabolism Brain Neoplasms - pathology Brain tumors Cancer therapies Cell Line, Tumor Central nervous system Chondroitin Sulfate Proteoglycans - biosynthesis Endothelial cells Ethics Female Fetus - metabolism Fetus - pathology Gene Expression Regulation, Neoplastic Glioblastoma Glioblastoma - metabolism Glioblastoma - pathology Glioblastoma cells Glucose Humans Isoforms Male Medicine Membrane Proteins - biosynthesis Mice Mice, Inbred BALB C Monoclonal antibodies Neoplasm Proteins - biosynthesis Neurosciences Neurosurgery Oncology Pericytes Pericytes - metabolism Pericytes - pathology Pleomorphism Protein Isoforms - biosynthesis Rodents Stem cells Tissues Tumor cell lines Tumors |
| title | Diversified expression of NG2/CSPG4 isoforms in glioblastoma and human foetal brain identifies pericyte subsets |
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