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Spontaneous In Vitro Transformation of Adult Neural Precursors into Stem-Like Cancer Cells
Recent studies have found that cellular self‐renewal capacity in brain cancer is heterogeneous, with only stem‐like cells having this property. A link between adult stem cells and cancer stem cells remains, however, to be shown. Here, we describe the emergence of cancer stem‐like cells from in vitro...
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| Published in: | Brain pathology (Zurich, Switzerland) Switzerland), 2009-07, Vol.19 (3), p.399-408 |
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| container_title | Brain pathology (Zurich, Switzerland) |
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| creator | Siebzehnrubl, Florian A. Jeske, Ina Müller, Dorit Buslei, Rolf Coras, Roland Hahnen, Eric Huttner, Hagen B. Corbeil, Denis Kaesbauer, Johanna Appl, Thomas Von Hörsten, Stephan Blümcke, Ingmar |
| description | Recent studies have found that cellular self‐renewal capacity in brain cancer is heterogeneous, with only stem‐like cells having this property. A link between adult stem cells and cancer stem cells remains, however, to be shown. Here, we describe the emergence of cancer stem‐like cells from in vitro cultured brain stem cells. Adult rat subventricular zone (SVZ) stem cells transformed into tumorigenic cell lines after expansion in vitro. These cell lines maintained characteristic features of stem‐like cells expressing Nestin, Musashi‐1 and CD133, but continued to proliferate upon differentiation induction. Karyotyping detected multiple acquired chromosomal aberrations, and syngeneic transplantation into the brain of adult rats resulted in malignant tumor formation. Tumors revealed streak necrosis and displayed a neural as well as an undifferentiated phenotype. Deficient downregulation of platelet‐derived growth factor (PDGF) receptor alpha was identified as candidate mechanism for tumor cell proliferation, and its knockdown by siRNA resulted in a reduction of cell growth. Our data point to adult brain precursor cells to be transformed in malignancies. Furthermore, in vitro expansion of adult neural stem cells, which will be mandatory for therapeutic strategies in neurological disorders, also harbors the risk for amplifying precursor cells with acquired genetic abnormalities and induction of malignant tumors after transplantation. |
| doi_str_mv | 10.1111/j.1750-3639.2008.00189.x |
| format | article |
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A link between adult stem cells and cancer stem cells remains, however, to be shown. Here, we describe the emergence of cancer stem‐like cells from in vitro cultured brain stem cells. Adult rat subventricular zone (SVZ) stem cells transformed into tumorigenic cell lines after expansion in vitro. These cell lines maintained characteristic features of stem‐like cells expressing Nestin, Musashi‐1 and CD133, but continued to proliferate upon differentiation induction. Karyotyping detected multiple acquired chromosomal aberrations, and syngeneic transplantation into the brain of adult rats resulted in malignant tumor formation. Tumors revealed streak necrosis and displayed a neural as well as an undifferentiated phenotype. Deficient downregulation of platelet‐derived growth factor (PDGF) receptor alpha was identified as candidate mechanism for tumor cell proliferation, and its knockdown by siRNA resulted in a reduction of cell growth. Our data point to adult brain precursor cells to be transformed in malignancies. Furthermore, in vitro expansion of adult neural stem cells, which will be mandatory for therapeutic strategies in neurological disorders, also harbors the risk for amplifying precursor cells with acquired genetic abnormalities and induction of malignant tumors after transplantation.</description><identifier>ISSN: 1015-6305</identifier><identifier>EISSN: 1750-3639</identifier><identifier>DOI: 10.1111/j.1750-3639.2008.00189.x</identifier><identifier>PMID: 18637011</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>adult stem cells ; Adult Stem Cells - pathology ; Animals ; Blotting, Western ; Brain - cytology ; Brain Neoplasms - genetics ; Brain Neoplasms - pathology ; Brain Tissue Transplantation - adverse effects ; carcinogenesis ; Cell Differentiation - physiology ; Cell Transformation, Neoplastic - genetics ; Cell Transformation, Neoplastic - pathology ; Chromosome Aberrations ; CNS ; Immunohistochemistry ; Neoplastic Stem Cells - pathology ; Neurons - pathology ; Rats ; Rats, Wistar ; Receptor, Platelet-Derived Growth Factor alpha - genetics ; Receptor, Platelet-Derived Growth Factor alpha - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Small Interfering ; Transfection ; transplantation ; tumor formation ; tumorigenesis</subject><ispartof>Brain pathology (Zurich, Switzerland), 2009-07, Vol.19 (3), p.399-408</ispartof><rights>2008 The Authors; Journal Compilation © 2008 International Society of Neuropathology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5409-79982d9059d03b739412154c51dfaba74d65667f3da31788ff471d6b9a1d79d23</citedby><cites>FETCH-LOGICAL-c5409-79982d9059d03b739412154c51dfaba74d65667f3da31788ff471d6b9a1d79d23</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/PMC8094744/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094744/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18637011$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Siebzehnrubl, Florian A.</creatorcontrib><creatorcontrib>Jeske, Ina</creatorcontrib><creatorcontrib>Müller, Dorit</creatorcontrib><creatorcontrib>Buslei, Rolf</creatorcontrib><creatorcontrib>Coras, Roland</creatorcontrib><creatorcontrib>Hahnen, Eric</creatorcontrib><creatorcontrib>Huttner, Hagen B.</creatorcontrib><creatorcontrib>Corbeil, Denis</creatorcontrib><creatorcontrib>Kaesbauer, Johanna</creatorcontrib><creatorcontrib>Appl, Thomas</creatorcontrib><creatorcontrib>Von Hörsten, Stephan</creatorcontrib><creatorcontrib>Blümcke, Ingmar</creatorcontrib><title>Spontaneous In Vitro Transformation of Adult Neural Precursors into Stem-Like Cancer Cells</title><title>Brain pathology (Zurich, Switzerland)</title><addtitle>Brain Pathol</addtitle><description>Recent studies have found that cellular self‐renewal capacity in brain cancer is heterogeneous, with only stem‐like cells having this property. A link between adult stem cells and cancer stem cells remains, however, to be shown. Here, we describe the emergence of cancer stem‐like cells from in vitro cultured brain stem cells. Adult rat subventricular zone (SVZ) stem cells transformed into tumorigenic cell lines after expansion in vitro. These cell lines maintained characteristic features of stem‐like cells expressing Nestin, Musashi‐1 and CD133, but continued to proliferate upon differentiation induction. Karyotyping detected multiple acquired chromosomal aberrations, and syngeneic transplantation into the brain of adult rats resulted in malignant tumor formation. Tumors revealed streak necrosis and displayed a neural as well as an undifferentiated phenotype. Deficient downregulation of platelet‐derived growth factor (PDGF) receptor alpha was identified as candidate mechanism for tumor cell proliferation, and its knockdown by siRNA resulted in a reduction of cell growth. Our data point to adult brain precursor cells to be transformed in malignancies. Furthermore, in vitro expansion of adult neural stem cells, which will be mandatory for therapeutic strategies in neurological disorders, also harbors the risk for amplifying precursor cells with acquired genetic abnormalities and induction of malignant tumors after transplantation.</description><subject>adult stem cells</subject><subject>Adult Stem Cells - pathology</subject><subject>Animals</subject><subject>Blotting, Western</subject><subject>Brain - cytology</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - pathology</subject><subject>Brain Tissue Transplantation - adverse effects</subject><subject>carcinogenesis</subject><subject>Cell Differentiation - physiology</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Cell Transformation, Neoplastic - pathology</subject><subject>Chromosome Aberrations</subject><subject>CNS</subject><subject>Immunohistochemistry</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Neurons - pathology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptor, Platelet-Derived Growth Factor alpha - genetics</subject><subject>Receptor, Platelet-Derived Growth Factor alpha - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Small Interfering</subject><subject>Transfection</subject><subject>transplantation</subject><subject>tumor formation</subject><subject>tumorigenesis</subject><issn>1015-6305</issn><issn>1750-3639</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><recordid>eNqNUcGO0zAQtRCIXRZ-AfnELcGO49iWEFKpYFmpKittAWkvIzd2wN0k7toJdP8eh1QFbvjikea9NzPvIYQpyWl6r3c5FZxkrGIqLwiROSFUqvzwCJ2fGo9TTSjPKkb4GXoW4y6BVKX4U3RGZcUEofQc3d7sfT_o3vox4qsef3FD8HgTdB8bHzo9ON9j3-CFGdsBr-0YdIuvg63HEH2I2PWDxzeD7bKVu7N4qfvaBry0bRufoyeNbqN9cfwv0OcP7zfLj9nq0-XVcrHKal4SlQmlZGEU4coQthVMlbSgvKw5NY3ealGaileVaJjRjAopm6YU1FRbpakRyhTsAr2ddffjtrOmtv2QloR9cJ0OD-C1g387vfsO3_wPkESVoiyTwKujQPD3o40DdC7W6YTZFiiSubLk0yQ5A-vgYwy2OQ2hBKZgYAeT_zD5D1Mw8DsYOCTqy7-X_EM8JpEAb2bAT9fah_8WhnfXi1QkejbTXRzs4UTX4Q4qwQSHr-tLoGu6WctbCor9AgjFrAM</recordid><startdate>200907</startdate><enddate>200907</enddate><creator>Siebzehnrubl, Florian A.</creator><creator>Jeske, Ina</creator><creator>Müller, Dorit</creator><creator>Buslei, Rolf</creator><creator>Coras, Roland</creator><creator>Hahnen, Eric</creator><creator>Huttner, Hagen B.</creator><creator>Corbeil, Denis</creator><creator>Kaesbauer, Johanna</creator><creator>Appl, Thomas</creator><creator>Von Hörsten, Stephan</creator><creator>Blümcke, Ingmar</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><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>7TK</scope><scope>5PM</scope></search><sort><creationdate>200907</creationdate><title>Spontaneous In Vitro Transformation of Adult Neural Precursors into Stem-Like Cancer Cells</title><author>Siebzehnrubl, Florian A. ; Jeske, Ina ; Müller, Dorit ; Buslei, Rolf ; Coras, Roland ; Hahnen, Eric ; Huttner, Hagen B. ; Corbeil, Denis ; Kaesbauer, Johanna ; Appl, Thomas ; Von Hörsten, Stephan ; Blümcke, Ingmar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5409-79982d9059d03b739412154c51dfaba74d65667f3da31788ff471d6b9a1d79d23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>adult stem cells</topic><topic>Adult Stem Cells - pathology</topic><topic>Animals</topic><topic>Blotting, Western</topic><topic>Brain - cytology</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - pathology</topic><topic>Brain Tissue Transplantation - adverse effects</topic><topic>carcinogenesis</topic><topic>Cell Differentiation - physiology</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>Cell Transformation, Neoplastic - pathology</topic><topic>Chromosome Aberrations</topic><topic>CNS</topic><topic>Immunohistochemistry</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Neurons - pathology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptor, Platelet-Derived Growth Factor alpha - genetics</topic><topic>Receptor, Platelet-Derived Growth Factor alpha - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Small Interfering</topic><topic>Transfection</topic><topic>transplantation</topic><topic>tumor formation</topic><topic>tumorigenesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Siebzehnrubl, Florian A.</creatorcontrib><creatorcontrib>Jeske, Ina</creatorcontrib><creatorcontrib>Müller, Dorit</creatorcontrib><creatorcontrib>Buslei, Rolf</creatorcontrib><creatorcontrib>Coras, Roland</creatorcontrib><creatorcontrib>Hahnen, Eric</creatorcontrib><creatorcontrib>Huttner, Hagen B.</creatorcontrib><creatorcontrib>Corbeil, Denis</creatorcontrib><creatorcontrib>Kaesbauer, Johanna</creatorcontrib><creatorcontrib>Appl, Thomas</creatorcontrib><creatorcontrib>Von Hörsten, Stephan</creatorcontrib><creatorcontrib>Blümcke, Ingmar</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Brain pathology (Zurich, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Siebzehnrubl, Florian A.</au><au>Jeske, Ina</au><au>Müller, Dorit</au><au>Buslei, Rolf</au><au>Coras, Roland</au><au>Hahnen, Eric</au><au>Huttner, Hagen B.</au><au>Corbeil, Denis</au><au>Kaesbauer, Johanna</au><au>Appl, Thomas</au><au>Von Hörsten, Stephan</au><au>Blümcke, Ingmar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Spontaneous In Vitro Transformation of Adult Neural Precursors into Stem-Like Cancer Cells</atitle><jtitle>Brain pathology (Zurich, Switzerland)</jtitle><addtitle>Brain Pathol</addtitle><date>2009-07</date><risdate>2009</risdate><volume>19</volume><issue>3</issue><spage>399</spage><epage>408</epage><pages>399-408</pages><issn>1015-6305</issn><eissn>1750-3639</eissn><abstract>Recent studies have found that cellular self‐renewal capacity in brain cancer is heterogeneous, with only stem‐like cells having this property. A link between adult stem cells and cancer stem cells remains, however, to be shown. Here, we describe the emergence of cancer stem‐like cells from in vitro cultured brain stem cells. Adult rat subventricular zone (SVZ) stem cells transformed into tumorigenic cell lines after expansion in vitro. These cell lines maintained characteristic features of stem‐like cells expressing Nestin, Musashi‐1 and CD133, but continued to proliferate upon differentiation induction. Karyotyping detected multiple acquired chromosomal aberrations, and syngeneic transplantation into the brain of adult rats resulted in malignant tumor formation. Tumors revealed streak necrosis and displayed a neural as well as an undifferentiated phenotype. Deficient downregulation of platelet‐derived growth factor (PDGF) receptor alpha was identified as candidate mechanism for tumor cell proliferation, and its knockdown by siRNA resulted in a reduction of cell growth. 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| ispartof | Brain pathology (Zurich, Switzerland), 2009-07, Vol.19 (3), p.399-408 |
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| subjects | adult stem cells Adult Stem Cells - pathology Animals Blotting, Western Brain - cytology Brain Neoplasms - genetics Brain Neoplasms - pathology Brain Tissue Transplantation - adverse effects carcinogenesis Cell Differentiation - physiology Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - pathology Chromosome Aberrations CNS Immunohistochemistry Neoplastic Stem Cells - pathology Neurons - pathology Rats Rats, Wistar Receptor, Platelet-Derived Growth Factor alpha - genetics Receptor, Platelet-Derived Growth Factor alpha - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA, Small Interfering Transfection transplantation tumor formation tumorigenesis |
| title | Spontaneous In Vitro Transformation of Adult Neural Precursors into Stem-Like Cancer Cells |
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