Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade
Cancers are a heterogeneous mix of cells, some of which exhibit cancer stem cell-like characteristics including ATP-dependent drug efflux and elevated tumorigenic potential. To determine whether aerodigestive squamous cell carcinomas (SCCs) contain a subpopulation of cancer stem cell-like cells, we...
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| Veröffentlicht in: | British journal of cancer 2008-01, Vol.98 (2), p.380-387 |
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| creator | Loebinger, M R Giangreco, A Groot, K R Prichard, L Allen, K Simpson, C Bazley, L Navani, N Tibrewal, S Davies, D Janes, S M |
| description | Cancers are a heterogeneous mix of cells, some of which exhibit cancer stem cell-like characteristics including ATP-dependent drug efflux and elevated tumorigenic potential. To determine whether aerodigestive squamous cell carcinomas (SCCs) contain a subpopulation of cancer stem cell-like cells, we performed Hoechst dye efflux assays using four independent cell lines. Results revealed the presence of a rare, drug effluxing stem cell-like side population (SP) of cells within all cell lines tested (SCC-SP cells). These cells resembled previously characterised epithelial stem cells, and SCC-SP cell abundance was positively correlated with overall cellular density and individual cell quiescence. Serial SCC-SP fractionation and passaging increased their relative abundance within the total cell population. Purified SCC-SP cells also exhibited increased clonogenic potential in secondary cultures and enhanced tumorigenicity
in vivo
. Despite this, SCC-SP cells remained chemotherapeutically sensitive upon ATP-dependent transporter inhibition. Overall, these findings suggest that the existence of ATP transporter-dependent cancer stem-like cells may be relatively common, particularly within established tumours. Future chemotherapeutic strategies should therefore consider coupling identification and targeting of this potential stem cell-like population with standard treatment methodologies. |
| doi_str_mv | 10.1038/sj.bjc.6604185 |
| format | Article |
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in vivo
. Despite this, SCC-SP cells remained chemotherapeutically sensitive upon ATP-dependent transporter inhibition. Overall, these findings suggest that the existence of ATP transporter-dependent cancer stem-like cells may be relatively common, particularly within established tumours. Future chemotherapeutic strategies should therefore consider coupling identification and targeting of this potential stem cell-like population with standard treatment methodologies.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/sj.bjc.6604185</identifier><identifier>PMID: 18219291</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>ABC transporters ; Animals ; Antineoplastic Agents - pharmacology ; ATP Binding Cassette Transporter, Subfamily G, Member 2 ; ATP-Binding Cassette Transporters - antagonists & inhibitors ; ATP-Binding Cassette Transporters - genetics ; ATP-Binding Cassette Transporters - metabolism ; Biological and medical sciences ; Biomarkers, Tumor - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Cell Count ; Cell Line, Tumor ; Cell Proliferation ; Cell Separation ; Drug Resistance ; Drug Resistance, Neoplasm - drug effects ; Drug Resistance, Neoplasm - genetics ; Epidemiology ; Genotype & phenotype ; Humans ; Male ; Medical research ; Medical sciences ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Molecular Medicine ; Multidrug Resistance-Associated Proteins - genetics ; Multidrug Resistance-Associated Proteins - metabolism ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; Neoplastic Stem Cells - drug effects ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - pathology ; Neuroblastoma ; Oncology ; Pollutants ; Stem cells ; Translational Therapeutics ; Tumors ; Verapamil - pharmacology ; Xenograft Model Antitumor Assays</subject><ispartof>British journal of cancer, 2008-01, Vol.98 (2), p.380-387</ispartof><rights>The Author(s) 2008</rights><rights>2008 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Jan 29, 2008</rights><rights>Copyright © 2008 Cancer Research UK 2008 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c507t-d8614aef1448600ca48c797d7aaaea4d45eb0b26a864d129d395d724864a2abd3</citedby><cites>FETCH-LOGICAL-c507t-d8614aef1448600ca48c797d7aaaea4d45eb0b26a864d129d395d724864a2abd3</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/PMC2361447/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361447/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,2727,27924,27925,41488,42557,51319,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20143350$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18219291$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Loebinger, M R</creatorcontrib><creatorcontrib>Giangreco, A</creatorcontrib><creatorcontrib>Groot, K R</creatorcontrib><creatorcontrib>Prichard, L</creatorcontrib><creatorcontrib>Allen, K</creatorcontrib><creatorcontrib>Simpson, C</creatorcontrib><creatorcontrib>Bazley, L</creatorcontrib><creatorcontrib>Navani, N</creatorcontrib><creatorcontrib>Tibrewal, S</creatorcontrib><creatorcontrib>Davies, D</creatorcontrib><creatorcontrib>Janes, S M</creatorcontrib><title>Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Cancers are a heterogeneous mix of cells, some of which exhibit cancer stem cell-like characteristics including ATP-dependent drug efflux and elevated tumorigenic potential. To determine whether aerodigestive squamous cell carcinomas (SCCs) contain a subpopulation of cancer stem cell-like cells, we performed Hoechst dye efflux assays using four independent cell lines. Results revealed the presence of a rare, drug effluxing stem cell-like side population (SP) of cells within all cell lines tested (SCC-SP cells). These cells resembled previously characterised epithelial stem cells, and SCC-SP cell abundance was positively correlated with overall cellular density and individual cell quiescence. Serial SCC-SP fractionation and passaging increased their relative abundance within the total cell population. Purified SCC-SP cells also exhibited increased clonogenic potential in secondary cultures and enhanced tumorigenicity
in vivo
. Despite this, SCC-SP cells remained chemotherapeutically sensitive upon ATP-dependent transporter inhibition. Overall, these findings suggest that the existence of ATP transporter-dependent cancer stem-like cells may be relatively common, particularly within established tumours. Future chemotherapeutic strategies should therefore consider coupling identification and targeting of this potential stem cell-like population with standard treatment methodologies.</description><subject>ABC transporters</subject><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>ATP Binding Cassette Transporter, Subfamily G, Member 2</subject><subject>ATP-Binding Cassette Transporters - antagonists & inhibitors</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>ATP-Binding Cassette Transporters - metabolism</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell Count</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cell Separation</subject><subject>Drug Resistance</subject><subject>Drug Resistance, Neoplasm - drug effects</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Epidemiology</subject><subject>Genotype & phenotype</subject><subject>Humans</subject><subject>Male</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Molecular Medicine</subject><subject>Multidrug Resistance-Associated Proteins - genetics</subject><subject>Multidrug Resistance-Associated Proteins - metabolism</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Neoplastic Stem Cells - drug effects</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Neuroblastoma</subject><subject>Oncology</subject><subject>Pollutants</subject><subject>Stem cells</subject><subject>Translational Therapeutics</subject><subject>Tumors</subject><subject>Verapamil - pharmacology</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kc1v1DAQxSMEokvhyg1kIZVbtrbjxMkFqaz4kipxAM7WxJl0nSb21nYqVfzz9bJhC0icrNH7zfObmSx7yeia0aI-D8O6HfS6qqhgdfkoW7Gy4DmruXycrSilMqcNpyfZsxCGVDa0lk-zk6Szhjdslf38djPD5OZANI4j0WA1-lQ4G8FYAiSYDsnO7eYRonGWuJ6EiFM-mmv81RNI3EIk4JFMkFi9xckFtMFEc4ukvSMX7zckerBh53xET9rR6euEPs-e9DAGfLG8p9mPjx--bz7nl18_fdlcXOa6pDLmXV0xAdgzIeqKUg2i1rKRnQQABNGJElva8grqSnSMN13RlJ3kCRbAoe2K0-zdwXc3txN2Gm1KM6qdNxP4O-XAqL8Va7bqyt0qXqSfhUwGbxcD725mDFFNJuxnB4tpdUpSLiopygS--Qcc3OxtGk5x3jQNK-UeWh8g7V0IHvtjEkbV_qgqDCodVS1HTQ2v_8z_gC9XTMDZAkDQMPZp19qEI8cpE0VR0sSdH7iQJHuF_iHef79-deiwEGePR8vf-j1UB8b7</recordid><startdate>20080129</startdate><enddate>20080129</enddate><creator>Loebinger, M R</creator><creator>Giangreco, A</creator><creator>Groot, K R</creator><creator>Prichard, L</creator><creator>Allen, K</creator><creator>Simpson, C</creator><creator>Bazley, L</creator><creator>Navani, N</creator><creator>Tibrewal, S</creator><creator>Davies, D</creator><creator>Janes, S M</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>IQODW</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>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20080129</creationdate><title>Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade</title><author>Loebinger, M R ; Giangreco, A ; Groot, K R ; Prichard, L ; Allen, K ; Simpson, C ; Bazley, L ; Navani, N ; Tibrewal, S ; Davies, D ; Janes, S M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c507t-d8614aef1448600ca48c797d7aaaea4d45eb0b26a864d129d395d724864a2abd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>ABC transporters</topic><topic>Animals</topic><topic>Antineoplastic Agents - 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genetics</topic><topic>Multidrug Resistance-Associated Proteins - metabolism</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Neoplastic Stem Cells - drug effects</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Neuroblastoma</topic><topic>Oncology</topic><topic>Pollutants</topic><topic>Stem cells</topic><topic>Translational Therapeutics</topic><topic>Tumors</topic><topic>Verapamil - pharmacology</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Loebinger, M R</creatorcontrib><creatorcontrib>Giangreco, A</creatorcontrib><creatorcontrib>Groot, K R</creatorcontrib><creatorcontrib>Prichard, L</creatorcontrib><creatorcontrib>Allen, K</creatorcontrib><creatorcontrib>Simpson, C</creatorcontrib><creatorcontrib>Bazley, L</creatorcontrib><creatorcontrib>Navani, N</creatorcontrib><creatorcontrib>Tibrewal, S</creatorcontrib><creatorcontrib>Davies, D</creatorcontrib><creatorcontrib>Janes, S M</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</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>ProQuest SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</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>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Loebinger, M R</au><au>Giangreco, A</au><au>Groot, K R</au><au>Prichard, L</au><au>Allen, K</au><au>Simpson, C</au><au>Bazley, L</au><au>Navani, N</au><au>Tibrewal, S</au><au>Davies, D</au><au>Janes, S M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2008-01-29</date><risdate>2008</risdate><volume>98</volume><issue>2</issue><spage>380</spage><epage>387</epage><pages>380-387</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Cancers are a heterogeneous mix of cells, some of which exhibit cancer stem cell-like characteristics including ATP-dependent drug efflux and elevated tumorigenic potential. To determine whether aerodigestive squamous cell carcinomas (SCCs) contain a subpopulation of cancer stem cell-like cells, we performed Hoechst dye efflux assays using four independent cell lines. Results revealed the presence of a rare, drug effluxing stem cell-like side population (SP) of cells within all cell lines tested (SCC-SP cells). These cells resembled previously characterised epithelial stem cells, and SCC-SP cell abundance was positively correlated with overall cellular density and individual cell quiescence. Serial SCC-SP fractionation and passaging increased their relative abundance within the total cell population. Purified SCC-SP cells also exhibited increased clonogenic potential in secondary cultures and enhanced tumorigenicity
in vivo
. Despite this, SCC-SP cells remained chemotherapeutically sensitive upon ATP-dependent transporter inhibition. Overall, these findings suggest that the existence of ATP transporter-dependent cancer stem-like cells may be relatively common, particularly within established tumours. Future chemotherapeutic strategies should therefore consider coupling identification and targeting of this potential stem cell-like population with standard treatment methodologies.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>18219291</pmid><doi>10.1038/sj.bjc.6604185</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | ABC transporters Animals Antineoplastic Agents - pharmacology ATP Binding Cassette Transporter, Subfamily G, Member 2 ATP-Binding Cassette Transporters - antagonists & inhibitors ATP-Binding Cassette Transporters - genetics ATP-Binding Cassette Transporters - metabolism Biological and medical sciences Biomarkers, Tumor - metabolism Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Cell Count Cell Line, Tumor Cell Proliferation Cell Separation Drug Resistance Drug Resistance, Neoplasm - drug effects Drug Resistance, Neoplasm - genetics Epidemiology Genotype & phenotype Humans Male Medical research Medical sciences Mice Mice, Inbred NOD Mice, SCID Molecular Medicine Multidrug Resistance-Associated Proteins - genetics Multidrug Resistance-Associated Proteins - metabolism Neoplasm Proteins - genetics Neoplasm Proteins - metabolism Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - metabolism Neoplastic Stem Cells - pathology Neuroblastoma Oncology Pollutants Stem cells Translational Therapeutics Tumors Verapamil - pharmacology Xenograft Model Antitumor Assays |
| title | Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade |
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