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Enhanced expression of cancer testis antigen genes in glioma stem cells
Cancer stem cells are an important target for effective therapy, since they show tumorigenicity, chemoresistance, and radioresistance. We isolated cancer stem cells from glioma cell lines and tissues and examined the expression of cancer testis antigen (CTA) genes as potential target molecules for c...
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Published in: | Molecular carcinogenesis 2010-06, Vol.49 (6), p.532-544 |
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container_end_page | 544 |
container_issue | 6 |
container_start_page | 532 |
container_title | Molecular carcinogenesis |
container_volume | 49 |
creator | Yawata, Toshio Nakai, Eiichi Park, Kae Chang Chihara, Takahiro Kumazawa, Ayano Toyonaga, Shinichi Masahira, Takanori Nakabayashi, Hiromichi Kaji, Takao Shimizu, Keiji |
description | Cancer stem cells are an important target for effective therapy, since they show tumorigenicity, chemoresistance, and radioresistance. We isolated cancer stem cells from glioma cell lines and tissues and examined the expression of cancer testis antigen (CTA) genes as potential target molecules for cancer vaccine therapy. CTA genes were highly and frequently expressed in cancer stem cells compared with differentiated cells. In addition, histone acetylation levels in the promoter regions of CTA genes were high in cancer stem cells and low in differentiated cells, while DNA methylation analysis of the promoter regions revealed hypomethylation in cancer stem cells. This epigenetic difference between cells leads to heterogeneous expression of CTA genes in the tumor mass, which consists of cells at various levels of differentiation. Moreover, the expression level of HLA class I antigens was not affected by the differentiation status, suggesting that CTA genes may present as surface antigens in cancer stem cells. Taken together, these findings suggest that CTA genes may be attractive candidates for targeted vaccine therapy against cancer stem cells in glioma patients. © 2010 Wiley‐Liss, Inc. |
doi_str_mv | 10.1002/mc.20614 |
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We isolated cancer stem cells from glioma cell lines and tissues and examined the expression of cancer testis antigen (CTA) genes as potential target molecules for cancer vaccine therapy. CTA genes were highly and frequently expressed in cancer stem cells compared with differentiated cells. In addition, histone acetylation levels in the promoter regions of CTA genes were high in cancer stem cells and low in differentiated cells, while DNA methylation analysis of the promoter regions revealed hypomethylation in cancer stem cells. This epigenetic difference between cells leads to heterogeneous expression of CTA genes in the tumor mass, which consists of cells at various levels of differentiation. Moreover, the expression level of HLA class I antigens was not affected by the differentiation status, suggesting that CTA genes may present as surface antigens in cancer stem cells. Taken together, these findings suggest that CTA genes may be attractive candidates for targeted vaccine therapy against cancer stem cells in glioma patients. © 2010 Wiley‐Liss, Inc.</description><identifier>ISSN: 0899-1987</identifier><identifier>EISSN: 1098-2744</identifier><identifier>DOI: 10.1002/mc.20614</identifier><identifier>PMID: 20082319</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Acetylation ; Aged ; Animals ; Antigens, Neoplasm - genetics ; cancer stem cells ; Cell Differentiation ; Cell Line, Tumor ; DNA Methylation ; Epigenesis, Genetic ; epigenetics ; Female ; Gene Expression Regulation, Neoplastic ; Genes, MHC Class I ; Glioma - genetics ; Glioma - immunology ; Histones - metabolism ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Neoplasm Proteins - genetics ; Neoplastic Stem Cells - cytology ; Neoplastic Stem Cells - immunology ; Neoplastic Stem Cells - metabolism ; Promoter Regions, Genetic</subject><ispartof>Molecular carcinogenesis, 2010-06, Vol.49 (6), p.532-544</ispartof><rights>Copyright © 2010 Wiley‐Liss, Inc.</rights><rights>(c) 2010 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4564-e98721537de1c0f8ceb389b19ff81561448d5bca8dc2f4995e989bec7dadefb43</citedby><cites>FETCH-LOGICAL-c4564-e98721537de1c0f8ceb389b19ff81561448d5bca8dc2f4995e989bec7dadefb43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20082319$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yawata, Toshio</creatorcontrib><creatorcontrib>Nakai, Eiichi</creatorcontrib><creatorcontrib>Park, Kae Chang</creatorcontrib><creatorcontrib>Chihara, Takahiro</creatorcontrib><creatorcontrib>Kumazawa, Ayano</creatorcontrib><creatorcontrib>Toyonaga, Shinichi</creatorcontrib><creatorcontrib>Masahira, Takanori</creatorcontrib><creatorcontrib>Nakabayashi, Hiromichi</creatorcontrib><creatorcontrib>Kaji, Takao</creatorcontrib><creatorcontrib>Shimizu, Keiji</creatorcontrib><title>Enhanced expression of cancer testis antigen genes in glioma stem cells</title><title>Molecular carcinogenesis</title><addtitle>Mol. Carcinog</addtitle><description>Cancer stem cells are an important target for effective therapy, since they show tumorigenicity, chemoresistance, and radioresistance. We isolated cancer stem cells from glioma cell lines and tissues and examined the expression of cancer testis antigen (CTA) genes as potential target molecules for cancer vaccine therapy. CTA genes were highly and frequently expressed in cancer stem cells compared with differentiated cells. In addition, histone acetylation levels in the promoter regions of CTA genes were high in cancer stem cells and low in differentiated cells, while DNA methylation analysis of the promoter regions revealed hypomethylation in cancer stem cells. This epigenetic difference between cells leads to heterogeneous expression of CTA genes in the tumor mass, which consists of cells at various levels of differentiation. Moreover, the expression level of HLA class I antigens was not affected by the differentiation status, suggesting that CTA genes may present as surface antigens in cancer stem cells. Taken together, these findings suggest that CTA genes may be attractive candidates for targeted vaccine therapy against cancer stem cells in glioma patients. © 2010 Wiley‐Liss, Inc.</description><subject>Acetylation</subject><subject>Aged</subject><subject>Animals</subject><subject>Antigens, Neoplasm - genetics</subject><subject>cancer stem cells</subject><subject>Cell Differentiation</subject><subject>Cell Line, Tumor</subject><subject>DNA Methylation</subject><subject>Epigenesis, Genetic</subject><subject>epigenetics</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes, MHC Class I</subject><subject>Glioma - genetics</subject><subject>Glioma - immunology</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Middle Aged</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplastic Stem Cells - cytology</subject><subject>Neoplastic Stem Cells - immunology</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Promoter Regions, Genetic</subject><issn>0899-1987</issn><issn>1098-2744</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNqNkE1LAzEQhoMotlbBXyC56WVrskl2k6OUtiqtXpQeQzY7q9H9qJsW239vaj9ugodhhuGZl3dehC4p6VNC4tvK9mOSUH6EupQoGcUp58eoS6RSEVUy7aAz7z8IoTQV5BR1YkJkzKjqovGwfje1hRzDat6C966pcVNgu1m2eAF-4Tw29cK9QY1DgccuDKVrKoP9AipsoSz9OTopTOnhYtd76HU0fBncR5Pn8cPgbhJZLhIeQTATU8HSHKglhbSQMakyqopCUhE-4DIXmTUyt3HBlRLhQGVg09zkUGSc9dD1VnfeNl_L4E5Xzm8cmBqapdep4EIkQv2DZIxSpoKZHrrZkrZtvG-h0PPWVaZda0r0Jl9dWf2bb0CvdqLLrIL8AO4DDUC0Bb5dCes_hfR0sBfc8S5kuTrwpv3UScpSoWdPYy1mCXkcJVM9YD9Gs5Hp</recordid><startdate>201006</startdate><enddate>201006</enddate><creator>Yawata, Toshio</creator><creator>Nakai, Eiichi</creator><creator>Park, Kae Chang</creator><creator>Chihara, Takahiro</creator><creator>Kumazawa, Ayano</creator><creator>Toyonaga, Shinichi</creator><creator>Masahira, Takanori</creator><creator>Nakabayashi, Hiromichi</creator><creator>Kaji, Takao</creator><creator>Shimizu, Keiji</creator><general>Wiley Subscription Services, Inc., A Wiley Company</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>7X8</scope><scope>7QO</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>201006</creationdate><title>Enhanced expression of cancer testis antigen genes in glioma stem cells</title><author>Yawata, Toshio ; Nakai, Eiichi ; Park, Kae Chang ; Chihara, Takahiro ; Kumazawa, Ayano ; Toyonaga, Shinichi ; Masahira, Takanori ; Nakabayashi, Hiromichi ; Kaji, Takao ; Shimizu, Keiji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4564-e98721537de1c0f8ceb389b19ff81561448d5bca8dc2f4995e989bec7dadefb43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acetylation</topic><topic>Aged</topic><topic>Animals</topic><topic>Antigens, Neoplasm - genetics</topic><topic>cancer stem cells</topic><topic>Cell Differentiation</topic><topic>Cell Line, Tumor</topic><topic>DNA Methylation</topic><topic>Epigenesis, Genetic</topic><topic>epigenetics</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes, MHC Class I</topic><topic>Glioma - genetics</topic><topic>Glioma - immunology</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Middle Aged</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplastic Stem Cells - cytology</topic><topic>Neoplastic Stem Cells - immunology</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Promoter Regions, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yawata, Toshio</creatorcontrib><creatorcontrib>Nakai, Eiichi</creatorcontrib><creatorcontrib>Park, Kae Chang</creatorcontrib><creatorcontrib>Chihara, Takahiro</creatorcontrib><creatorcontrib>Kumazawa, Ayano</creatorcontrib><creatorcontrib>Toyonaga, Shinichi</creatorcontrib><creatorcontrib>Masahira, Takanori</creatorcontrib><creatorcontrib>Nakabayashi, Hiromichi</creatorcontrib><creatorcontrib>Kaji, Takao</creatorcontrib><creatorcontrib>Shimizu, Keiji</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>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Molecular carcinogenesis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yawata, Toshio</au><au>Nakai, Eiichi</au><au>Park, Kae Chang</au><au>Chihara, Takahiro</au><au>Kumazawa, Ayano</au><au>Toyonaga, Shinichi</au><au>Masahira, Takanori</au><au>Nakabayashi, Hiromichi</au><au>Kaji, Takao</au><au>Shimizu, Keiji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enhanced expression of cancer testis antigen genes in glioma stem cells</atitle><jtitle>Molecular carcinogenesis</jtitle><addtitle>Mol. 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subjects | Acetylation Aged Animals Antigens, Neoplasm - genetics cancer stem cells Cell Differentiation Cell Line, Tumor DNA Methylation Epigenesis, Genetic epigenetics Female Gene Expression Regulation, Neoplastic Genes, MHC Class I Glioma - genetics Glioma - immunology Histones - metabolism Humans Male Mice Mice, Inbred BALB C Middle Aged Neoplasm Proteins - genetics Neoplastic Stem Cells - cytology Neoplastic Stem Cells - immunology Neoplastic Stem Cells - metabolism Promoter Regions, Genetic |
title | Enhanced expression of cancer testis antigen genes in glioma stem cells |
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