Glial progenitor-like phenotype in low-grade glioma and enhanced CD133-expression and neuronal lineage differentiation potential in high-grade glioma
While neurosphere- as well as xenograft tumor-initiating cells have been identified in gliomas, the resemblance between glioma cells and neural stem/progenitor cells as well as the prognostic value of stem/progenitor cell marker expression in glioma are poorly clarified. Viable glioma cells were cha...
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| Veröffentlicht in: | PloS one 2008-04, Vol.3 (4), p.e1936-e1936 |
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| creator | Rebetz, Johan Tian, Dongping Persson, Annette Widegren, Bengt Salford, Leif G Englund, Elisabet Gisselsson, David Fan, Xiaolong |
| description | While neurosphere- as well as xenograft tumor-initiating cells have been identified in gliomas, the resemblance between glioma cells and neural stem/progenitor cells as well as the prognostic value of stem/progenitor cell marker expression in glioma are poorly clarified.
Viable glioma cells were characterized for surface marker expression along the glial genesis hierarchy. Six low-grade and 17 high-grade glioma specimens were flow-cytometrically analyzed for markers characteristics of stem cells (CD133); glial progenitors (PDGFRalpha, A2B5, O4, and CD44); and late oligodendrocyte progenitors (O1). In parallel, the expression of glial fibrillary acidic protein (GFAP), synaptophysin and neuron-specific enolase (NSE) was immunohistochemically analyzed in fixed tissue specimens. Irrespective of the grade and morphological diagnosis of gliomas, glioma cells concomitantly expressed PDGFRalpha, A2B5, O4, CD44 and GFAP. In contrast, O1 was weakly expressed in all low-grade and the majority of high-grade glioma specimens analyzed. Co-expression of neuronal markers was observed in all high-grade, but not low-grade, glioma specimens analyzed. The rare CD133 expressing cells in low-grade glioma specimens typically co-expressed vessel endothelial marker CD31. In contrast, distinct CD133 expression profiles in up to 90% of CD45-negative glioma cells were observed in 12 of the 17 high-grade glioma specimens and the majority of these CD133 expressing cells were CD31 negative. The CD133 expression correlates inversely with length of patient survival. Surprisingly, cytogenetic analysis showed that gliomas contained normal and abnormal cell karyotypes with hitherto indistinguishable phenotype.
This study constitutes an important step towards clarification of lineage commitment and differentiation blockage of glioma cells. Our data suggest that glioma cells may resemble expansion of glial lineage progenitor cells with compromised differentiation capacity downstream of A2B5 and O4 expression. The concurrent expression of neuronal markers demonstrates that high-grade glioma cells are endowed with multi-lineage differentiation potential in vivo. Importantly, enhanced CD133 expression marks a poor prognosis in gliomas. |
| doi_str_mv | 10.1371/journal.pone.0001936 |
| format | Article |
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Viable glioma cells were characterized for surface marker expression along the glial genesis hierarchy. Six low-grade and 17 high-grade glioma specimens were flow-cytometrically analyzed for markers characteristics of stem cells (CD133); glial progenitors (PDGFRalpha, A2B5, O4, and CD44); and late oligodendrocyte progenitors (O1). In parallel, the expression of glial fibrillary acidic protein (GFAP), synaptophysin and neuron-specific enolase (NSE) was immunohistochemically analyzed in fixed tissue specimens. Irrespective of the grade and morphological diagnosis of gliomas, glioma cells concomitantly expressed PDGFRalpha, A2B5, O4, CD44 and GFAP. In contrast, O1 was weakly expressed in all low-grade and the majority of high-grade glioma specimens analyzed. Co-expression of neuronal markers was observed in all high-grade, but not low-grade, glioma specimens analyzed. The rare CD133 expressing cells in low-grade glioma specimens typically co-expressed vessel endothelial marker CD31. In contrast, distinct CD133 expression profiles in up to 90% of CD45-negative glioma cells were observed in 12 of the 17 high-grade glioma specimens and the majority of these CD133 expressing cells were CD31 negative. The CD133 expression correlates inversely with length of patient survival. Surprisingly, cytogenetic analysis showed that gliomas contained normal and abnormal cell karyotypes with hitherto indistinguishable phenotype.
This study constitutes an important step towards clarification of lineage commitment and differentiation blockage of glioma cells. Our data suggest that glioma cells may resemble expansion of glial lineage progenitor cells with compromised differentiation capacity downstream of A2B5 and O4 expression. The concurrent expression of neuronal markers demonstrates that high-grade glioma cells are endowed with multi-lineage differentiation potential in vivo. Importantly, enhanced CD133 expression marks a poor prognosis in gliomas.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0001936</identifier><identifier>PMID: 18398462</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>AC133 Antigen ; Analysis ; Antigens, CD - biosynthesis ; Basic Medicine ; Biomarkers ; Blockage ; Brain cancer ; Brain Neoplasms - metabolism ; Brain tumors ; CD44 antigen ; CD45 antigen ; Cell Biology/Gene Expression ; Cell Differentiation ; Cell Lineage ; Cell survival ; Cells (biology) ; Chromosomes ; Clinical Medicine ; Differentiation ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; Glial fibrillary acidic protein ; Glial stem cells ; Glioma ; Glioma - diagnosis ; Glioma - metabolism ; Glioma - pathology ; Glioma cells ; Gliomas ; Glycoproteins - biosynthesis ; Growth factors ; Humans ; Intermediate filament proteins ; Karyotypes ; Karyotyping ; Kirurgi ; Klinisk medicin ; Laboratories ; Medical and Health Sciences ; Medical Genetics ; Medical prognosis ; Medicin och hälsovetenskap ; Medicinsk genetik ; Medicinska och farmaceutiska grundvetenskaper ; Multiple sclerosis ; Neural stem cells ; Neuroglia - cytology ; Neuroglia - metabolism ; Neurologi ; Neurology ; Neuronal-glial interactions ; Neurons ; Neurons - metabolism ; Neurons - pathology ; Neurosurgery ; Oncology/Neuro-Oncology ; Peptides ; Phenotype ; Phosphopyruvate hydratase ; Progenitor cells ; Prognosis ; Stem cells ; Stem Cells - cytology ; Studies ; Surface markers ; Surgery ; Synaptophysin ; Tumors ; Xenografts</subject><ispartof>PloS one, 2008-04, Vol.3 (4), p.e1936-e1936</ispartof><rights>COPYRIGHT 2008 Public Library of Science</rights><rights>2008 Rebetz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Rebetz et al. 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c797t-9a3068fb0540f298fe836b8816a10d2d444d470cf4abd00f6dc9a4b64e3e314b3</citedby><cites>FETCH-LOGICAL-c797t-9a3068fb0540f298fe836b8816a10d2d444d470cf4abd00f6dc9a4b64e3e314b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2277459/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2277459/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,550,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18398462$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://lup.lub.lu.se/record/1531260$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><contributor>Aboody, Karen S.</contributor><creatorcontrib>Rebetz, Johan</creatorcontrib><creatorcontrib>Tian, Dongping</creatorcontrib><creatorcontrib>Persson, Annette</creatorcontrib><creatorcontrib>Widegren, Bengt</creatorcontrib><creatorcontrib>Salford, Leif G</creatorcontrib><creatorcontrib>Englund, Elisabet</creatorcontrib><creatorcontrib>Gisselsson, David</creatorcontrib><creatorcontrib>Fan, Xiaolong</creatorcontrib><title>Glial progenitor-like phenotype in low-grade glioma and enhanced CD133-expression and neuronal lineage differentiation potential in high-grade glioma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>While neurosphere- as well as xenograft tumor-initiating cells have been identified in gliomas, the resemblance between glioma cells and neural stem/progenitor cells as well as the prognostic value of stem/progenitor cell marker expression in glioma are poorly clarified.
Viable glioma cells were characterized for surface marker expression along the glial genesis hierarchy. Six low-grade and 17 high-grade glioma specimens were flow-cytometrically analyzed for markers characteristics of stem cells (CD133); glial progenitors (PDGFRalpha, A2B5, O4, and CD44); and late oligodendrocyte progenitors (O1). In parallel, the expression of glial fibrillary acidic protein (GFAP), synaptophysin and neuron-specific enolase (NSE) was immunohistochemically analyzed in fixed tissue specimens. Irrespective of the grade and morphological diagnosis of gliomas, glioma cells concomitantly expressed PDGFRalpha, A2B5, O4, CD44 and GFAP. In contrast, O1 was weakly expressed in all low-grade and the majority of high-grade glioma specimens analyzed. Co-expression of neuronal markers was observed in all high-grade, but not low-grade, glioma specimens analyzed. The rare CD133 expressing cells in low-grade glioma specimens typically co-expressed vessel endothelial marker CD31. In contrast, distinct CD133 expression profiles in up to 90% of CD45-negative glioma cells were observed in 12 of the 17 high-grade glioma specimens and the majority of these CD133 expressing cells were CD31 negative. The CD133 expression correlates inversely with length of patient survival. Surprisingly, cytogenetic analysis showed that gliomas contained normal and abnormal cell karyotypes with hitherto indistinguishable phenotype.
This study constitutes an important step towards clarification of lineage commitment and differentiation blockage of glioma cells. Our data suggest that glioma cells may resemble expansion of glial lineage progenitor cells with compromised differentiation capacity downstream of A2B5 and O4 expression. The concurrent expression of neuronal markers demonstrates that high-grade glioma cells are endowed with multi-lineage differentiation potential in vivo. Importantly, enhanced CD133 expression marks a poor prognosis in gliomas.</description><subject>AC133 Antigen</subject><subject>Analysis</subject><subject>Antigens, CD - biosynthesis</subject><subject>Basic Medicine</subject><subject>Biomarkers</subject><subject>Blockage</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - metabolism</subject><subject>Brain tumors</subject><subject>CD44 antigen</subject><subject>CD45 antigen</subject><subject>Cell Biology/Gene Expression</subject><subject>Cell Differentiation</subject><subject>Cell Lineage</subject><subject>Cell survival</subject><subject>Cells (biology)</subject><subject>Chromosomes</subject><subject>Clinical Medicine</subject><subject>Differentiation</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic aspects</subject><subject>Glial fibrillary acidic protein</subject><subject>Glial stem cells</subject><subject>Glioma</subject><subject>Glioma - diagnosis</subject><subject>Glioma - metabolism</subject><subject>Glioma - pathology</subject><subject>Glioma cells</subject><subject>Gliomas</subject><subject>Glycoproteins - biosynthesis</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Intermediate filament proteins</subject><subject>Karyotypes</subject><subject>Karyotyping</subject><subject>Kirurgi</subject><subject>Klinisk medicin</subject><subject>Laboratories</subject><subject>Medical and Health Sciences</subject><subject>Medical Genetics</subject><subject>Medical prognosis</subject><subject>Medicin och hälsovetenskap</subject><subject>Medicinsk genetik</subject><subject>Medicinska och farmaceutiska grundvetenskaper</subject><subject>Multiple sclerosis</subject><subject>Neural stem cells</subject><subject>Neuroglia - cytology</subject><subject>Neuroglia - metabolism</subject><subject>Neurologi</subject><subject>Neurology</subject><subject>Neuronal-glial interactions</subject><subject>Neurons</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>Neurosurgery</subject><subject>Oncology/Neuro-Oncology</subject><subject>Peptides</subject><subject>Phenotype</subject><subject>Phosphopyruvate hydratase</subject><subject>Progenitor cells</subject><subject>Prognosis</subject><subject>Stem cells</subject><subject>Stem Cells - cytology</subject><subject>Studies</subject><subject>Surface markers</subject><subject>Surgery</subject><subject>Synaptophysin</subject><subject>Tumors</subject><subject>Xenografts</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>D8T</sourceid><sourceid>DOA</sourceid><recordid>eNqNk21r1TAUx4sobk6_gWhBGPii1zw1Td8I46pzMBj49Dak7UmbmZvUpHXbB_H7mrt71VV8ISHk6Xf-J_mTk2VPMVphWuFXl34OTtnV6B2sEEK4pvxedpgGUnCC6P0784PsUYyXCJVUcP4wO8CC1oJxcpj9OLVG2XwMvgdnJh8Ka75CPg7g_HQzQm5cbv1V0QfVQd5b4zcqV67LwQ3KtdDl6zeY0gKuxwAxGu9uTx3Mwafb5dY4UD3kndEaArjJqGkLjX66XdhtgsH0wyLD4-yBVjbCk_14lH1-9_bT-n1xfnF6tj45L9qqrqaiVhRxoRtUMqRJLTQIyhshMFcYdaRjjHWsQq1mqukQ0rxra8UazoACxayhR9nzne5ofZR7R6PEFBOCSE3LRJztiM6rSzkGs1HhRnpl5O2GD71UYTKtBalIqzHumGANSkkqURKmKsE1MKxKIEnrfKcVr2Ccm4WancfUm9RlBNm2RHeiwrKpFZJMNEzWSpeSJ32VnldSqJLc6_3l52YDXZv8DMouVJcnzgyy998lIVXFyjoJHO8Fgv82Q5zkxsQWrFUO_BxlhVhdCsET-OIv8N9WrXZUr5IbxmmfsrapdbAxbfql2qT9E1YRXjJGtrIvFwGJmeB66tUcozz7-OH_2YsvS_b4DjuAstMQvZ23Hy8uQbYD2-BjDKB_m4eR3BbZr3fKbZHJfZGlsGd3jf8TtK8q-hMRyiSb</recordid><startdate>20080409</startdate><enddate>20080409</enddate><creator>Rebetz, Johan</creator><creator>Tian, Dongping</creator><creator>Persson, Annette</creator><creator>Widegren, Bengt</creator><creator>Salford, Leif G</creator><creator>Englund, Elisabet</creator><creator>Gisselsson, David</creator><creator>Fan, Xiaolong</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AGCHP</scope><scope>AOWAS</scope><scope>D8T</scope><scope>D95</scope><scope>ZZAVC</scope><scope>DOA</scope></search><sort><creationdate>20080409</creationdate><title>Glial progenitor-like phenotype in low-grade glioma and enhanced CD133-expression and neuronal lineage differentiation potential in high-grade glioma</title><author>Rebetz, Johan ; Tian, Dongping ; Persson, Annette ; Widegren, Bengt ; Salford, Leif G ; Englund, Elisabet ; Gisselsson, David ; Fan, Xiaolong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c797t-9a3068fb0540f298fe836b8816a10d2d444d470cf4abd00f6dc9a4b64e3e314b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>AC133 Antigen</topic><topic>Analysis</topic><topic>Antigens, CD - biosynthesis</topic><topic>Basic Medicine</topic><topic>Biomarkers</topic><topic>Blockage</topic><topic>Brain cancer</topic><topic>Brain Neoplasms - metabolism</topic><topic>Brain tumors</topic><topic>CD44 antigen</topic><topic>CD45 antigen</topic><topic>Cell Biology/Gene Expression</topic><topic>Cell Differentiation</topic><topic>Cell Lineage</topic><topic>Cell survival</topic><topic>Cells (biology)</topic><topic>Chromosomes</topic><topic>Clinical Medicine</topic><topic>Differentiation</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genetic aspects</topic><topic>Glial fibrillary acidic protein</topic><topic>Glial stem cells</topic><topic>Glioma</topic><topic>Glioma - diagnosis</topic><topic>Glioma - metabolism</topic><topic>Glioma - pathology</topic><topic>Glioma cells</topic><topic>Gliomas</topic><topic>Glycoproteins - biosynthesis</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Intermediate filament proteins</topic><topic>Karyotypes</topic><topic>Karyotyping</topic><topic>Kirurgi</topic><topic>Klinisk medicin</topic><topic>Laboratories</topic><topic>Medical and Health Sciences</topic><topic>Medical Genetics</topic><topic>Medical prognosis</topic><topic>Medicin och hälsovetenskap</topic><topic>Medicinsk genetik</topic><topic>Medicinska och farmaceutiska grundvetenskaper</topic><topic>Multiple sclerosis</topic><topic>Neural stem cells</topic><topic>Neuroglia - cytology</topic><topic>Neuroglia - metabolism</topic><topic>Neurologi</topic><topic>Neurology</topic><topic>Neuronal-glial interactions</topic><topic>Neurons</topic><topic>Neurons - metabolism</topic><topic>Neurons - pathology</topic><topic>Neurosurgery</topic><topic>Oncology/Neuro-Oncology</topic><topic>Peptides</topic><topic>Phenotype</topic><topic>Phosphopyruvate hydratase</topic><topic>Progenitor cells</topic><topic>Prognosis</topic><topic>Stem cells</topic><topic>Stem Cells - cytology</topic><topic>Studies</topic><topic>Surface markers</topic><topic>Surgery</topic><topic>Synaptophysin</topic><topic>Tumors</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rebetz, Johan</creatorcontrib><creatorcontrib>Tian, Dongping</creatorcontrib><creatorcontrib>Persson, Annette</creatorcontrib><creatorcontrib>Widegren, Bengt</creatorcontrib><creatorcontrib>Salford, Leif G</creatorcontrib><creatorcontrib>Englund, Elisabet</creatorcontrib><creatorcontrib>Gisselsson, David</creatorcontrib><creatorcontrib>Fan, Xiaolong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SWEPUB Lunds universitet full text</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SWEPUB Lunds universitet</collection><collection>SwePub Articles full text</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>Rebetz, Johan</au><au>Tian, Dongping</au><au>Persson, Annette</au><au>Widegren, Bengt</au><au>Salford, Leif G</au><au>Englund, Elisabet</au><au>Gisselsson, David</au><au>Fan, Xiaolong</au><au>Aboody, Karen S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glial progenitor-like phenotype in low-grade glioma and enhanced CD133-expression and neuronal lineage differentiation potential in high-grade glioma</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2008-04-09</date><risdate>2008</risdate><volume>3</volume><issue>4</issue><spage>e1936</spage><epage>e1936</epage><pages>e1936-e1936</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>While neurosphere- as well as xenograft tumor-initiating cells have been identified in gliomas, the resemblance between glioma cells and neural stem/progenitor cells as well as the prognostic value of stem/progenitor cell marker expression in glioma are poorly clarified.
Viable glioma cells were characterized for surface marker expression along the glial genesis hierarchy. Six low-grade and 17 high-grade glioma specimens were flow-cytometrically analyzed for markers characteristics of stem cells (CD133); glial progenitors (PDGFRalpha, A2B5, O4, and CD44); and late oligodendrocyte progenitors (O1). In parallel, the expression of glial fibrillary acidic protein (GFAP), synaptophysin and neuron-specific enolase (NSE) was immunohistochemically analyzed in fixed tissue specimens. Irrespective of the grade and morphological diagnosis of gliomas, glioma cells concomitantly expressed PDGFRalpha, A2B5, O4, CD44 and GFAP. In contrast, O1 was weakly expressed in all low-grade and the majority of high-grade glioma specimens analyzed. Co-expression of neuronal markers was observed in all high-grade, but not low-grade, glioma specimens analyzed. The rare CD133 expressing cells in low-grade glioma specimens typically co-expressed vessel endothelial marker CD31. In contrast, distinct CD133 expression profiles in up to 90% of CD45-negative glioma cells were observed in 12 of the 17 high-grade glioma specimens and the majority of these CD133 expressing cells were CD31 negative. The CD133 expression correlates inversely with length of patient survival. Surprisingly, cytogenetic analysis showed that gliomas contained normal and abnormal cell karyotypes with hitherto indistinguishable phenotype.
This study constitutes an important step towards clarification of lineage commitment and differentiation blockage of glioma cells. Our data suggest that glioma cells may resemble expansion of glial lineage progenitor cells with compromised differentiation capacity downstream of A2B5 and O4 expression. The concurrent expression of neuronal markers demonstrates that high-grade glioma cells are endowed with multi-lineage differentiation potential in vivo. Importantly, enhanced CD133 expression marks a poor prognosis in gliomas.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>18398462</pmid><doi>10.1371/journal.pone.0001936</doi><tpages>e1936</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2008-04, Vol.3 (4), p.e1936-e1936 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1312202935 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; SWEPUB Freely available online; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | AC133 Antigen Analysis Antigens, CD - biosynthesis Basic Medicine Biomarkers Blockage Brain cancer Brain Neoplasms - metabolism Brain tumors CD44 antigen CD45 antigen Cell Biology/Gene Expression Cell Differentiation Cell Lineage Cell survival Cells (biology) Chromosomes Clinical Medicine Differentiation Gene expression Gene Expression Regulation, Neoplastic Genetic aspects Glial fibrillary acidic protein Glial stem cells Glioma Glioma - diagnosis Glioma - metabolism Glioma - pathology Glioma cells Gliomas Glycoproteins - biosynthesis Growth factors Humans Intermediate filament proteins Karyotypes Karyotyping Kirurgi Klinisk medicin Laboratories Medical and Health Sciences Medical Genetics Medical prognosis Medicin och hälsovetenskap Medicinsk genetik Medicinska och farmaceutiska grundvetenskaper Multiple sclerosis Neural stem cells Neuroglia - cytology Neuroglia - metabolism Neurologi Neurology Neuronal-glial interactions Neurons Neurons - metabolism Neurons - pathology Neurosurgery Oncology/Neuro-Oncology Peptides Phenotype Phosphopyruvate hydratase Progenitor cells Prognosis Stem cells Stem Cells - cytology Studies Surface markers Surgery Synaptophysin Tumors Xenografts |
| title | Glial progenitor-like phenotype in low-grade glioma and enhanced CD133-expression and neuronal lineage differentiation potential in high-grade glioma |
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