Cancer stem cell traits in squamospheres derived from primary head and neck squamous cell carcinomas
Summary A subpopulation of cancer stem cells (CSCs), but not the majority of non-tumorigenic cancer cells, in a variety of human malignancies plays a critical role in cancer cell proliferation, invasion, metastasis, and tumor recurrence post-therapies. We report the isolation of sphere-forming cells...
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| Veröffentlicht in: | Oral oncology 2011-02, Vol.47 (2), p.83-91 |
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| creator | Lim, Young Chang Oh, Se-Yeong Cha, Yun Yi Kim, Sung-Hak Jin, Xun Kim, Hyunggee |
| description | Summary A subpopulation of cancer stem cells (CSCs), but not the majority of non-tumorigenic cancer cells, in a variety of human malignancies plays a critical role in cancer cell proliferation, invasion, metastasis, and tumor recurrence post-therapies. We report the isolation of sphere-forming cells (squamospheres) from primary head and neck squamous cell carcinomas (HNSCCs), and characterization of their CSC properties. Squamospheres appeared within 2 weeks after seeding as single-dissociated cells obtained from primary HNSCC specimens in serum-free culture conditions. Real-time RT-PCR and immunocytochemistry assays revealed that a number of stem cell markers, including CK5, OCT4, SOX2, and nestin, were up-regulated in HNSCC-driven squamospheres. Fluorescence-activated cell sorting (FACS) analysis showed that squamospheres contain enriched side population cells compared to serum-induced differentiated squamosphere cells. Furthermore, HNSCC-driven squamospheres appeared to be chemoresistant to cisplatin, 5-fluorouracil (FU), paclitaxel and doxetaxel, and showed increased levels of ABCG2, one of the ATP-binding cassette (ABC) transporters. Of particular interest, in sharp contrast to subcutaneous injection of 1 × 106 differentiated squamosphere cells, as few as 100 squamosphere cells were able to give rise to tumors in nude mice. Altogether, we assert that primary HNSCC-driven squamospheres possess CSC properties, and its functional analysis may provide a novel tool for investigating the tumorigenic process of HNSCC. |
| doi_str_mv | 10.1016/j.oraloncology.2010.11.011 |
| format | Article |
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We report the isolation of sphere-forming cells (squamospheres) from primary head and neck squamous cell carcinomas (HNSCCs), and characterization of their CSC properties. Squamospheres appeared within 2 weeks after seeding as single-dissociated cells obtained from primary HNSCC specimens in serum-free culture conditions. Real-time RT-PCR and immunocytochemistry assays revealed that a number of stem cell markers, including CK5, OCT4, SOX2, and nestin, were up-regulated in HNSCC-driven squamospheres. Fluorescence-activated cell sorting (FACS) analysis showed that squamospheres contain enriched side population cells compared to serum-induced differentiated squamosphere cells. Furthermore, HNSCC-driven squamospheres appeared to be chemoresistant to cisplatin, 5-fluorouracil (FU), paclitaxel and doxetaxel, and showed increased levels of ABCG2, one of the ATP-binding cassette (ABC) transporters. Of particular interest, in sharp contrast to subcutaneous injection of 1 × 106 differentiated squamosphere cells, as few as 100 squamosphere cells were able to give rise to tumors in nude mice. Altogether, we assert that primary HNSCC-driven squamospheres possess CSC properties, and its functional analysis may provide a novel tool for investigating the tumorigenic process of HNSCC.</description><identifier>ISSN: 1368-8375</identifier><identifier>EISSN: 1879-0593</identifier><identifier>DOI: 10.1016/j.oraloncology.2010.11.011</identifier><identifier>PMID: 21167769</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Animals ; Biological and medical sciences ; Carcinoma - metabolism ; Carcinoma - pathology ; Carcinoma, Squamous Cell ; Cell Line, Tumor ; Cell Proliferation ; Female ; Flow Cytometry ; Fluorouracil ; Head and neck neoplasms ; Head and Neck Neoplasms - metabolism ; Head and Neck Neoplasms - pathology ; Hematology, Oncology and Palliative Medicine ; Humans ; Intermediate Filament Proteins - metabolism ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Proteins - metabolism ; Neoplasms, Squamous Cell - metabolism ; Neoplasms, Squamous Cell - pathology ; Neoplastic stem cells ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - pathology ; Nerve Tissue Proteins - metabolism ; Nestin ; Oral cancer ; Otolaryngology ; Otorhinolaryngology (head neck, general aspects and miscellaneous) ; Otorhinolaryngology. Stomatology ; Reverse Transcriptase Polymerase Chain Reaction ; Spheroids, Cellular - metabolism ; Spheroids, Cellular - pathology ; Squamospheres ; Squamous Cell Carcinoma of Head and Neck ; Tumors ; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</subject><ispartof>Oral oncology, 2011-02, Vol.47 (2), p.83-91</ispartof><rights>Elsevier Ltd</rights><rights>2010 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-8342cebbb4e0abf05235d05129e4efb6455857ac8835e61b1e4568a8ff8fa2293</citedby><cites>FETCH-LOGICAL-c464t-8342cebbb4e0abf05235d05129e4efb6455857ac8835e61b1e4568a8ff8fa2293</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1368837510003623$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23870577$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21167769$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lim, Young Chang</creatorcontrib><creatorcontrib>Oh, Se-Yeong</creatorcontrib><creatorcontrib>Cha, Yun Yi</creatorcontrib><creatorcontrib>Kim, Sung-Hak</creatorcontrib><creatorcontrib>Jin, Xun</creatorcontrib><creatorcontrib>Kim, Hyunggee</creatorcontrib><title>Cancer stem cell traits in squamospheres derived from primary head and neck squamous cell carcinomas</title><title>Oral oncology</title><addtitle>Oral Oncol</addtitle><description>Summary A subpopulation of cancer stem cells (CSCs), but not the majority of non-tumorigenic cancer cells, in a variety of human malignancies plays a critical role in cancer cell proliferation, invasion, metastasis, and tumor recurrence post-therapies. We report the isolation of sphere-forming cells (squamospheres) from primary head and neck squamous cell carcinomas (HNSCCs), and characterization of their CSC properties. Squamospheres appeared within 2 weeks after seeding as single-dissociated cells obtained from primary HNSCC specimens in serum-free culture conditions. Real-time RT-PCR and immunocytochemistry assays revealed that a number of stem cell markers, including CK5, OCT4, SOX2, and nestin, were up-regulated in HNSCC-driven squamospheres. Fluorescence-activated cell sorting (FACS) analysis showed that squamospheres contain enriched side population cells compared to serum-induced differentiated squamosphere cells. Furthermore, HNSCC-driven squamospheres appeared to be chemoresistant to cisplatin, 5-fluorouracil (FU), paclitaxel and doxetaxel, and showed increased levels of ABCG2, one of the ATP-binding cassette (ABC) transporters. Of particular interest, in sharp contrast to subcutaneous injection of 1 × 106 differentiated squamosphere cells, as few as 100 squamosphere cells were able to give rise to tumors in nude mice. Altogether, we assert that primary HNSCC-driven squamospheres possess CSC properties, and its functional analysis may provide a novel tool for investigating the tumorigenic process of HNSCC.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Carcinoma - metabolism</subject><subject>Carcinoma - pathology</subject><subject>Carcinoma, Squamous Cell</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Fluorouracil</subject><subject>Head and neck neoplasms</subject><subject>Head and Neck Neoplasms - metabolism</subject><subject>Head and Neck Neoplasms - pathology</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Intermediate Filament Proteins - metabolism</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Neoplasms, Squamous Cell - metabolism</subject><subject>Neoplasms, Squamous Cell - pathology</subject><subject>Neoplastic stem cells</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Nestin</subject><subject>Oral cancer</subject><subject>Otolaryngology</subject><subject>Otorhinolaryngology (head neck, general aspects and miscellaneous)</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Spheroids, Cellular - metabolism</subject><subject>Spheroids, Cellular - pathology</subject><subject>Squamospheres</subject><subject>Squamous Cell Carcinoma of Head and Neck</subject><subject>Tumors</subject><subject>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</subject><issn>1368-8375</issn><issn>1879-0593</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkk1v1DAQhiMEoqXwF5CFhDjt4o_YcTggVQsFpEocgLPl2GPqbRJvPUml_fc42lAQJ0625GfGrx9PVb1idMsoU2_325Rtn0aX-vTzuOV0OWBbytij6pzppt1Q2YrHZS-U3mjRyLPqGeKeUiqZpE-rM86YahrVnld-Z0cHmeAEA3HQ92TKNk5I4kjwbrZDwsMNZEDiIcd78CTkNJBDjoPNR3ID1hM7ejKCu10LZjw1cja7OKbB4vPqSbA9wot1vah-XH38vvu8uf766cvu8nrjalVPJWnNHXRdVwO1XaCSC-lLZN5CDaFTtZRaNtZpLSQo1jGopdJWh6CD5bwVF9WbU99DTncz4GSGiEsWO0KJZbSkUjHBeSHfnUiXE2KGYNYXGUbNItnszd-SzSLZMGaK5FL8cr1m7gbwD6W_rRbg9QpYdLYPuTiO-IcTuqGyaQr34cRBkXIfIRt0Ecp_-JjBTcan-H953v_TxvVxjOXmWzgC7tOcx6LdMIPcUPNtGYtlKlgZCKG4EL8An3O38g</recordid><startdate>20110201</startdate><enddate>20110201</enddate><creator>Lim, Young Chang</creator><creator>Oh, Se-Yeong</creator><creator>Cha, Yun Yi</creator><creator>Kim, Sung-Hak</creator><creator>Jin, Xun</creator><creator>Kim, Hyunggee</creator><general>Elsevier Ltd</general><general>Elsevier</general><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>7X8</scope></search><sort><creationdate>20110201</creationdate><title>Cancer stem cell traits in squamospheres derived from primary head and neck squamous cell carcinomas</title><author>Lim, Young Chang ; Oh, Se-Yeong ; Cha, Yun Yi ; Kim, Sung-Hak ; Jin, Xun ; Kim, Hyunggee</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c464t-8342cebbb4e0abf05235d05129e4efb6455857ac8835e61b1e4568a8ff8fa2293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Carcinoma - metabolism</topic><topic>Carcinoma - pathology</topic><topic>Carcinoma, Squamous Cell</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Fluorouracil</topic><topic>Head and neck neoplasms</topic><topic>Head and Neck Neoplasms - metabolism</topic><topic>Head and Neck Neoplasms - pathology</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Intermediate Filament Proteins - metabolism</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Neoplasms, Squamous Cell - metabolism</topic><topic>Neoplasms, Squamous Cell - pathology</topic><topic>Neoplastic stem cells</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Nestin</topic><topic>Oral cancer</topic><topic>Otolaryngology</topic><topic>Otorhinolaryngology (head neck, general aspects and miscellaneous)</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Spheroids, Cellular - metabolism</topic><topic>Spheroids, Cellular - pathology</topic><topic>Squamospheres</topic><topic>Squamous Cell Carcinoma of Head and Neck</topic><topic>Tumors</topic><topic>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lim, Young Chang</creatorcontrib><creatorcontrib>Oh, Se-Yeong</creatorcontrib><creatorcontrib>Cha, Yun Yi</creatorcontrib><creatorcontrib>Kim, Sung-Hak</creatorcontrib><creatorcontrib>Jin, Xun</creatorcontrib><creatorcontrib>Kim, Hyunggee</creatorcontrib><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>MEDLINE - Academic</collection><jtitle>Oral oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lim, Young Chang</au><au>Oh, Se-Yeong</au><au>Cha, Yun Yi</au><au>Kim, Sung-Hak</au><au>Jin, Xun</au><au>Kim, Hyunggee</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cancer stem cell traits in squamospheres derived from primary head and neck squamous cell carcinomas</atitle><jtitle>Oral oncology</jtitle><addtitle>Oral Oncol</addtitle><date>2011-02-01</date><risdate>2011</risdate><volume>47</volume><issue>2</issue><spage>83</spage><epage>91</epage><pages>83-91</pages><issn>1368-8375</issn><eissn>1879-0593</eissn><abstract>Summary A subpopulation of cancer stem cells (CSCs), but not the majority of non-tumorigenic cancer cells, in a variety of human malignancies plays a critical role in cancer cell proliferation, invasion, metastasis, and tumor recurrence post-therapies. We report the isolation of sphere-forming cells (squamospheres) from primary head and neck squamous cell carcinomas (HNSCCs), and characterization of their CSC properties. Squamospheres appeared within 2 weeks after seeding as single-dissociated cells obtained from primary HNSCC specimens in serum-free culture conditions. Real-time RT-PCR and immunocytochemistry assays revealed that a number of stem cell markers, including CK5, OCT4, SOX2, and nestin, were up-regulated in HNSCC-driven squamospheres. Fluorescence-activated cell sorting (FACS) analysis showed that squamospheres contain enriched side population cells compared to serum-induced differentiated squamosphere cells. Furthermore, HNSCC-driven squamospheres appeared to be chemoresistant to cisplatin, 5-fluorouracil (FU), paclitaxel and doxetaxel, and showed increased levels of ABCG2, one of the ATP-binding cassette (ABC) transporters. Of particular interest, in sharp contrast to subcutaneous injection of 1 × 106 differentiated squamosphere cells, as few as 100 squamosphere cells were able to give rise to tumors in nude mice. Altogether, we assert that primary HNSCC-driven squamospheres possess CSC properties, and its functional analysis may provide a novel tool for investigating the tumorigenic process of HNSCC.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>21167769</pmid><doi>10.1016/j.oraloncology.2010.11.011</doi><tpages>9</tpages></addata></record> |
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| subjects | Animals Biological and medical sciences Carcinoma - metabolism Carcinoma - pathology Carcinoma, Squamous Cell Cell Line, Tumor Cell Proliferation Female Flow Cytometry Fluorouracil Head and neck neoplasms Head and Neck Neoplasms - metabolism Head and Neck Neoplasms - pathology Hematology, Oncology and Palliative Medicine Humans Intermediate Filament Proteins - metabolism Medical sciences Mice Mice, Inbred BALB C Mice, Nude Neoplasm Proteins - metabolism Neoplasms, Squamous Cell - metabolism Neoplasms, Squamous Cell - pathology Neoplastic stem cells Neoplastic Stem Cells - metabolism Neoplastic Stem Cells - pathology Nerve Tissue Proteins - metabolism Nestin Oral cancer Otolaryngology Otorhinolaryngology (head neck, general aspects and miscellaneous) Otorhinolaryngology. Stomatology Reverse Transcriptase Polymerase Chain Reaction Spheroids, Cellular - metabolism Spheroids, Cellular - pathology Squamospheres Squamous Cell Carcinoma of Head and Neck Tumors Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology |
| title | Cancer stem cell traits in squamospheres derived from primary head and neck squamous cell carcinomas |
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