Glioma‐Associated Stem Cells: A Novel Class of Tumor‐Supporting Cells Able to Predict Prognosis of Human Low‐Grade Gliomas
Background: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low‐grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state‐of‐the‐art markers, hind...
Gespeichert in:
| Veröffentlicht in: | Stem cells (Dayton, Ohio) Ohio), 2014-05, Vol.32 (5), p.1239-1253 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1253 |
|---|---|
| container_issue | 5 |
| container_start_page | 1239 |
| container_title | Stem cells (Dayton, Ohio) |
| container_volume | 32 |
| creator | Bourkoula, Evgenia Mangoni, Damiano Ius, Tamara Pucer, Anja Isola, Miriam Musiello, Daniela Marzinotto, Stefania Toffoletto, Barbara Sorrentino, Marisa Palma, Anita Caponnetto, Federica Gregoraci, Giorgia Vindigni, Marco Pizzolitto, Stefano Falconieri, Giovanni Maglio, Giovanna Pecile, Vanna Ruaro, Maria Elisabetta Gri, Giorgia Parisse, Pietro Casalis, Loredana Scoles, Giacinto Skrap, Miran Beltrami, Carlo Alberto Beltrami, Antonio Paolo Cesselli, Daniela |
| description | Background: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low‐grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state‐of‐the‐art markers, hindering the decision‐making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high‐grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm. Methods and Findings: We isolated glioma‐associated stem cells (GASC) from LGG (n=40) and HGG (n=73). GASC showed stem cell features, anchorage‐independent growth, and supported the malignant properties of both A172 cells and human glioma‐stem cells, mainly through the release of exosomes. Finally, starting from GASC obtained from HGG (n=13) and LGG (n=12) we defined a score, based on the expression of 9 GASC surface markers, whose prognostic value was assayed on 40 subsequent LGG‐patients. At the multivariate Cox analysis, the GASC‐based score was the only independent predictor of overall survival and malignant progression free‐survival. Conclusions: The microenvironment of both LGG and HGG hosts non‐tumorigenic multipotent stem cells that can increase in vitro the biological aggressiveness of glioma‐initiating cells through the release of exosomes. The clinical importance of this finding is supported by the strong prognostic value associated with the characteristics of GASC. This patient‐based approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor stroma. Stem Cells 2014;32:1239–1253 |
| doi_str_mv | 10.1002/stem.1605 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1524419393</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3278895341</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4215-2578dffa9be4cb1596b714312d1d36355be3d575ed0d0085603a28f2527f0a313</originalsourceid><addsrcrecordid>eNqN0ctO3DAUBmALFQEFFrxAZambdhE4viU2u9EIhkrDRZphHTmxg4KSeLCTInY8As_Ik-CZ0C6QkFjZi-_8PtaP0BGBYwJAT0Jv22OSgthCe0RwlXBF5Ld4hzRNBCi1i76HcA9AuJByB-1SzjKRyWwPPc-a2rX69fllEoIra91bgxcxD09t04RTPMFX7q9t8LTRIWBX4eXQOh_9YlitnO_r7m6keFI0FvcO33hr6rKPp7vrXKg3UxdDqzs8d49xcua1sXh8OByg7Uo3wR6-n_vo9vxsOb1I5tezP9PJPCk5JSKhcV1TVVoVlpcFESotMsIZoYYYljIhCsuMyIQ1YACkSIFpKisqaFaBZoTto19j7sq7h8GGPm_rUMbFdWfdEHIiKOdEMcW-QEkmJaQKIv35gd67wXfxIxvFhQCpovo9qtK7ELyt8pWvW-2fcgL5usF83WC-bjDaH--JQ9Fa81_-qyyCkxE81o19-jwpXyzPLjeRb10VptI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1517455089</pqid></control><display><type>article</type><title>Glioma‐Associated Stem Cells: A Novel Class of Tumor‐Supporting Cells Able to Predict Prognosis of Human Low‐Grade Gliomas</title><source>MEDLINE</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Bourkoula, Evgenia ; Mangoni, Damiano ; Ius, Tamara ; Pucer, Anja ; Isola, Miriam ; Musiello, Daniela ; Marzinotto, Stefania ; Toffoletto, Barbara ; Sorrentino, Marisa ; Palma, Anita ; Caponnetto, Federica ; Gregoraci, Giorgia ; Vindigni, Marco ; Pizzolitto, Stefano ; Falconieri, Giovanni ; Maglio, Giovanna ; Pecile, Vanna ; Ruaro, Maria Elisabetta ; Gri, Giorgia ; Parisse, Pietro ; Casalis, Loredana ; Scoles, Giacinto ; Skrap, Miran ; Beltrami, Carlo Alberto ; Beltrami, Antonio Paolo ; Cesselli, Daniela</creator><creatorcontrib>Bourkoula, Evgenia ; Mangoni, Damiano ; Ius, Tamara ; Pucer, Anja ; Isola, Miriam ; Musiello, Daniela ; Marzinotto, Stefania ; Toffoletto, Barbara ; Sorrentino, Marisa ; Palma, Anita ; Caponnetto, Federica ; Gregoraci, Giorgia ; Vindigni, Marco ; Pizzolitto, Stefano ; Falconieri, Giovanni ; Maglio, Giovanna ; Pecile, Vanna ; Ruaro, Maria Elisabetta ; Gri, Giorgia ; Parisse, Pietro ; Casalis, Loredana ; Scoles, Giacinto ; Skrap, Miran ; Beltrami, Carlo Alberto ; Beltrami, Antonio Paolo ; Cesselli, Daniela</creatorcontrib><description>Background: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low‐grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state‐of‐the‐art markers, hindering the decision‐making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high‐grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm. Methods and Findings: We isolated glioma‐associated stem cells (GASC) from LGG (n=40) and HGG (n=73). GASC showed stem cell features, anchorage‐independent growth, and supported the malignant properties of both A172 cells and human glioma‐stem cells, mainly through the release of exosomes. Finally, starting from GASC obtained from HGG (n=13) and LGG (n=12) we defined a score, based on the expression of 9 GASC surface markers, whose prognostic value was assayed on 40 subsequent LGG‐patients. At the multivariate Cox analysis, the GASC‐based score was the only independent predictor of overall survival and malignant progression free‐survival. Conclusions: The microenvironment of both LGG and HGG hosts non‐tumorigenic multipotent stem cells that can increase in vitro the biological aggressiveness of glioma‐initiating cells through the release of exosomes. The clinical importance of this finding is supported by the strong prognostic value associated with the characteristics of GASC. This patient‐based approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor stroma. Stem Cells 2014;32:1239–1253</description><identifier>ISSN: 1066-5099</identifier><identifier>EISSN: 1549-4918</identifier><identifier>DOI: 10.1002/stem.1605</identifier><identifier>PMID: 24375787</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Adult ; Aged ; Brain Neoplasms - genetics ; Brain Neoplasms - metabolism ; Brain Neoplasms - pathology ; Cell Line ; Cell Proliferation ; Exosomes ; Exosomes - metabolism ; Female ; Gene Expression ; Glioma - genetics ; Glioma - metabolism ; Glioma - pathology ; Glioma‐associated stem cells ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Human glioma ; Humans ; Kaplan-Meier Estimate ; Low‐grade glioma ; Luminescent Proteins - genetics ; Luminescent Proteins - metabolism ; Male ; Medical prognosis ; Medical research ; Microscopy, Atomic Force ; Microscopy, Fluorescence ; Middle Aged ; Multivariate Analysis ; Nanog Homeobox Protein ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - pathology ; Octamer Transcription Factor-3 - genetics ; Octamer Transcription Factor-3 - metabolism ; Personalized medicine ; Prognosis ; Prognostic score ; Reverse Transcriptase Polymerase Chain Reaction ; Stem cells ; Tumor Cells, Cultured ; Tumor Microenvironment</subject><ispartof>Stem cells (Dayton, Ohio), 2014-05, Vol.32 (5), p.1239-1253</ispartof><rights>2013 AlphaMed Press</rights><rights>2013 AlphaMed Press.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4215-2578dffa9be4cb1596b714312d1d36355be3d575ed0d0085603a28f2527f0a313</citedby><cites>FETCH-LOGICAL-c4215-2578dffa9be4cb1596b714312d1d36355be3d575ed0d0085603a28f2527f0a313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24375787$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bourkoula, Evgenia</creatorcontrib><creatorcontrib>Mangoni, Damiano</creatorcontrib><creatorcontrib>Ius, Tamara</creatorcontrib><creatorcontrib>Pucer, Anja</creatorcontrib><creatorcontrib>Isola, Miriam</creatorcontrib><creatorcontrib>Musiello, Daniela</creatorcontrib><creatorcontrib>Marzinotto, Stefania</creatorcontrib><creatorcontrib>Toffoletto, Barbara</creatorcontrib><creatorcontrib>Sorrentino, Marisa</creatorcontrib><creatorcontrib>Palma, Anita</creatorcontrib><creatorcontrib>Caponnetto, Federica</creatorcontrib><creatorcontrib>Gregoraci, Giorgia</creatorcontrib><creatorcontrib>Vindigni, Marco</creatorcontrib><creatorcontrib>Pizzolitto, Stefano</creatorcontrib><creatorcontrib>Falconieri, Giovanni</creatorcontrib><creatorcontrib>Maglio, Giovanna</creatorcontrib><creatorcontrib>Pecile, Vanna</creatorcontrib><creatorcontrib>Ruaro, Maria Elisabetta</creatorcontrib><creatorcontrib>Gri, Giorgia</creatorcontrib><creatorcontrib>Parisse, Pietro</creatorcontrib><creatorcontrib>Casalis, Loredana</creatorcontrib><creatorcontrib>Scoles, Giacinto</creatorcontrib><creatorcontrib>Skrap, Miran</creatorcontrib><creatorcontrib>Beltrami, Carlo Alberto</creatorcontrib><creatorcontrib>Beltrami, Antonio Paolo</creatorcontrib><creatorcontrib>Cesselli, Daniela</creatorcontrib><title>Glioma‐Associated Stem Cells: A Novel Class of Tumor‐Supporting Cells Able to Predict Prognosis of Human Low‐Grade Gliomas</title><title>Stem cells (Dayton, Ohio)</title><addtitle>Stem Cells</addtitle><description>Background: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low‐grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state‐of‐the‐art markers, hindering the decision‐making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high‐grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm. Methods and Findings: We isolated glioma‐associated stem cells (GASC) from LGG (n=40) and HGG (n=73). GASC showed stem cell features, anchorage‐independent growth, and supported the malignant properties of both A172 cells and human glioma‐stem cells, mainly through the release of exosomes. Finally, starting from GASC obtained from HGG (n=13) and LGG (n=12) we defined a score, based on the expression of 9 GASC surface markers, whose prognostic value was assayed on 40 subsequent LGG‐patients. At the multivariate Cox analysis, the GASC‐based score was the only independent predictor of overall survival and malignant progression free‐survival. Conclusions: The microenvironment of both LGG and HGG hosts non‐tumorigenic multipotent stem cells that can increase in vitro the biological aggressiveness of glioma‐initiating cells through the release of exosomes. The clinical importance of this finding is supported by the strong prognostic value associated with the characteristics of GASC. This patient‐based approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor stroma. Stem Cells 2014;32:1239–1253</description><subject>Adult</subject><subject>Aged</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - metabolism</subject><subject>Brain Neoplasms - pathology</subject><subject>Cell Line</subject><subject>Cell Proliferation</subject><subject>Exosomes</subject><subject>Exosomes - metabolism</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Glioma - genetics</subject><subject>Glioma - metabolism</subject><subject>Glioma - pathology</subject><subject>Glioma‐associated stem cells</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Human glioma</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Low‐grade glioma</subject><subject>Luminescent Proteins - genetics</subject><subject>Luminescent Proteins - metabolism</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Microscopy, Atomic Force</subject><subject>Microscopy, Fluorescence</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Nanog Homeobox Protein</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Octamer Transcription Factor-3 - genetics</subject><subject>Octamer Transcription Factor-3 - metabolism</subject><subject>Personalized medicine</subject><subject>Prognosis</subject><subject>Prognostic score</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Stem cells</subject><subject>Tumor Cells, Cultured</subject><subject>Tumor Microenvironment</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0ctO3DAUBmALFQEFFrxAZambdhE4viU2u9EIhkrDRZphHTmxg4KSeLCTInY8As_Ik-CZ0C6QkFjZi-_8PtaP0BGBYwJAT0Jv22OSgthCe0RwlXBF5Ld4hzRNBCi1i76HcA9AuJByB-1SzjKRyWwPPc-a2rX69fllEoIra91bgxcxD09t04RTPMFX7q9t8LTRIWBX4eXQOh_9YlitnO_r7m6keFI0FvcO33hr6rKPp7vrXKg3UxdDqzs8d49xcua1sXh8OByg7Uo3wR6-n_vo9vxsOb1I5tezP9PJPCk5JSKhcV1TVVoVlpcFESotMsIZoYYYljIhCsuMyIQ1YACkSIFpKisqaFaBZoTto19j7sq7h8GGPm_rUMbFdWfdEHIiKOdEMcW-QEkmJaQKIv35gd67wXfxIxvFhQCpovo9qtK7ELyt8pWvW-2fcgL5usF83WC-bjDaH--JQ9Fa81_-qyyCkxE81o19-jwpXyzPLjeRb10VptI</recordid><startdate>201405</startdate><enddate>201405</enddate><creator>Bourkoula, Evgenia</creator><creator>Mangoni, Damiano</creator><creator>Ius, Tamara</creator><creator>Pucer, Anja</creator><creator>Isola, Miriam</creator><creator>Musiello, Daniela</creator><creator>Marzinotto, Stefania</creator><creator>Toffoletto, Barbara</creator><creator>Sorrentino, Marisa</creator><creator>Palma, Anita</creator><creator>Caponnetto, Federica</creator><creator>Gregoraci, Giorgia</creator><creator>Vindigni, Marco</creator><creator>Pizzolitto, Stefano</creator><creator>Falconieri, Giovanni</creator><creator>Maglio, Giovanna</creator><creator>Pecile, Vanna</creator><creator>Ruaro, Maria Elisabetta</creator><creator>Gri, Giorgia</creator><creator>Parisse, Pietro</creator><creator>Casalis, Loredana</creator><creator>Scoles, Giacinto</creator><creator>Skrap, Miran</creator><creator>Beltrami, Carlo Alberto</creator><creator>Beltrami, Antonio Paolo</creator><creator>Cesselli, Daniela</creator><general>Oxford University Press</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>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201405</creationdate><title>Glioma‐Associated Stem Cells: A Novel Class of Tumor‐Supporting Cells Able to Predict Prognosis of Human Low‐Grade Gliomas</title><author>Bourkoula, Evgenia ; Mangoni, Damiano ; Ius, Tamara ; Pucer, Anja ; Isola, Miriam ; Musiello, Daniela ; Marzinotto, Stefania ; Toffoletto, Barbara ; Sorrentino, Marisa ; Palma, Anita ; Caponnetto, Federica ; Gregoraci, Giorgia ; Vindigni, Marco ; Pizzolitto, Stefano ; Falconieri, Giovanni ; Maglio, Giovanna ; Pecile, Vanna ; Ruaro, Maria Elisabetta ; Gri, Giorgia ; Parisse, Pietro ; Casalis, Loredana ; Scoles, Giacinto ; Skrap, Miran ; Beltrami, Carlo Alberto ; Beltrami, Antonio Paolo ; Cesselli, Daniela</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4215-2578dffa9be4cb1596b714312d1d36355be3d575ed0d0085603a28f2527f0a313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - metabolism</topic><topic>Brain Neoplasms - pathology</topic><topic>Cell Line</topic><topic>Cell Proliferation</topic><topic>Exosomes</topic><topic>Exosomes - metabolism</topic><topic>Female</topic><topic>Gene Expression</topic><topic>Glioma - genetics</topic><topic>Glioma - metabolism</topic><topic>Glioma - pathology</topic><topic>Glioma‐associated stem cells</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Human glioma</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Low‐grade glioma</topic><topic>Luminescent Proteins - genetics</topic><topic>Luminescent Proteins - metabolism</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Microscopy, Atomic Force</topic><topic>Microscopy, Fluorescence</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Nanog Homeobox Protein</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Octamer Transcription Factor-3 - genetics</topic><topic>Octamer Transcription Factor-3 - metabolism</topic><topic>Personalized medicine</topic><topic>Prognosis</topic><topic>Prognostic score</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Stem cells</topic><topic>Tumor Cells, Cultured</topic><topic>Tumor Microenvironment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bourkoula, Evgenia</creatorcontrib><creatorcontrib>Mangoni, Damiano</creatorcontrib><creatorcontrib>Ius, Tamara</creatorcontrib><creatorcontrib>Pucer, Anja</creatorcontrib><creatorcontrib>Isola, Miriam</creatorcontrib><creatorcontrib>Musiello, Daniela</creatorcontrib><creatorcontrib>Marzinotto, Stefania</creatorcontrib><creatorcontrib>Toffoletto, Barbara</creatorcontrib><creatorcontrib>Sorrentino, Marisa</creatorcontrib><creatorcontrib>Palma, Anita</creatorcontrib><creatorcontrib>Caponnetto, Federica</creatorcontrib><creatorcontrib>Gregoraci, Giorgia</creatorcontrib><creatorcontrib>Vindigni, Marco</creatorcontrib><creatorcontrib>Pizzolitto, Stefano</creatorcontrib><creatorcontrib>Falconieri, Giovanni</creatorcontrib><creatorcontrib>Maglio, Giovanna</creatorcontrib><creatorcontrib>Pecile, Vanna</creatorcontrib><creatorcontrib>Ruaro, Maria Elisabetta</creatorcontrib><creatorcontrib>Gri, Giorgia</creatorcontrib><creatorcontrib>Parisse, Pietro</creatorcontrib><creatorcontrib>Casalis, Loredana</creatorcontrib><creatorcontrib>Scoles, Giacinto</creatorcontrib><creatorcontrib>Skrap, Miran</creatorcontrib><creatorcontrib>Beltrami, Carlo Alberto</creatorcontrib><creatorcontrib>Beltrami, Antonio Paolo</creatorcontrib><creatorcontrib>Cesselli, Daniela</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Stem cells (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bourkoula, Evgenia</au><au>Mangoni, Damiano</au><au>Ius, Tamara</au><au>Pucer, Anja</au><au>Isola, Miriam</au><au>Musiello, Daniela</au><au>Marzinotto, Stefania</au><au>Toffoletto, Barbara</au><au>Sorrentino, Marisa</au><au>Palma, Anita</au><au>Caponnetto, Federica</au><au>Gregoraci, Giorgia</au><au>Vindigni, Marco</au><au>Pizzolitto, Stefano</au><au>Falconieri, Giovanni</au><au>Maglio, Giovanna</au><au>Pecile, Vanna</au><au>Ruaro, Maria Elisabetta</au><au>Gri, Giorgia</au><au>Parisse, Pietro</au><au>Casalis, Loredana</au><au>Scoles, Giacinto</au><au>Skrap, Miran</au><au>Beltrami, Carlo Alberto</au><au>Beltrami, Antonio Paolo</au><au>Cesselli, Daniela</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glioma‐Associated Stem Cells: A Novel Class of Tumor‐Supporting Cells Able to Predict Prognosis of Human Low‐Grade Gliomas</atitle><jtitle>Stem cells (Dayton, Ohio)</jtitle><addtitle>Stem Cells</addtitle><date>2014-05</date><risdate>2014</risdate><volume>32</volume><issue>5</issue><spage>1239</spage><epage>1253</epage><pages>1239-1253</pages><issn>1066-5099</issn><eissn>1549-4918</eissn><abstract>Background: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low‐grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state‐of‐the‐art markers, hindering the decision‐making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high‐grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm. Methods and Findings: We isolated glioma‐associated stem cells (GASC) from LGG (n=40) and HGG (n=73). GASC showed stem cell features, anchorage‐independent growth, and supported the malignant properties of both A172 cells and human glioma‐stem cells, mainly through the release of exosomes. Finally, starting from GASC obtained from HGG (n=13) and LGG (n=12) we defined a score, based on the expression of 9 GASC surface markers, whose prognostic value was assayed on 40 subsequent LGG‐patients. At the multivariate Cox analysis, the GASC‐based score was the only independent predictor of overall survival and malignant progression free‐survival. Conclusions: The microenvironment of both LGG and HGG hosts non‐tumorigenic multipotent stem cells that can increase in vitro the biological aggressiveness of glioma‐initiating cells through the release of exosomes. The clinical importance of this finding is supported by the strong prognostic value associated with the characteristics of GASC. This patient‐based approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor stroma. Stem Cells 2014;32:1239–1253</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>24375787</pmid><doi>10.1002/stem.1605</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1066-5099 |
| ispartof | Stem cells (Dayton, Ohio), 2014-05, Vol.32 (5), p.1239-1253 |
| issn | 1066-5099 1549-4918 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1524419393 |
| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Aged Brain Neoplasms - genetics Brain Neoplasms - metabolism Brain Neoplasms - pathology Cell Line Cell Proliferation Exosomes Exosomes - metabolism Female Gene Expression Glioma - genetics Glioma - metabolism Glioma - pathology Glioma‐associated stem cells Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Human glioma Humans Kaplan-Meier Estimate Low‐grade glioma Luminescent Proteins - genetics Luminescent Proteins - metabolism Male Medical prognosis Medical research Microscopy, Atomic Force Microscopy, Fluorescence Middle Aged Multivariate Analysis Nanog Homeobox Protein Neoplastic Stem Cells - metabolism Neoplastic Stem Cells - pathology Octamer Transcription Factor-3 - genetics Octamer Transcription Factor-3 - metabolism Personalized medicine Prognosis Prognostic score Reverse Transcriptase Polymerase Chain Reaction Stem cells Tumor Cells, Cultured Tumor Microenvironment |
| title | Glioma‐Associated Stem Cells: A Novel Class of Tumor‐Supporting Cells Able to Predict Prognosis of Human Low‐Grade Gliomas |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T08%3A51%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Glioma%E2%80%90Associated%20Stem%20Cells:%20A%20Novel%20Class%20of%20Tumor%E2%80%90Supporting%20Cells%20Able%20to%20Predict%20Prognosis%20of%20Human%20Low%E2%80%90Grade%20Gliomas&rft.jtitle=Stem%20cells%20(Dayton,%20Ohio)&rft.au=Bourkoula,%20Evgenia&rft.date=2014-05&rft.volume=32&rft.issue=5&rft.spage=1239&rft.epage=1253&rft.pages=1239-1253&rft.issn=1066-5099&rft.eissn=1549-4918&rft_id=info:doi/10.1002/stem.1605&rft_dat=%3Cproquest_cross%3E3278895341%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1517455089&rft_id=info:pmid/24375787&rfr_iscdi=true |