The low-affinity nerve growth factor receptor p75NTR identifies a transient stem cell-like state in oral squamous cell carcinoma cells

Background Although several markers have been used for enrichment of cells with stem cell‐like properties in oral squamous cell carcinoma (OSCC), isolation of a pure subpopulation is still a challenging task. Normal oral and esophageal keratinocyte stem cells have been previously isolated using the...

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Veröffentlicht in:Journal of oral pathology & medicine 2015-07, Vol.44 (6), p.410-419
Hauptverfasser: Osman, Tarig A., Parajuli, Himalaya, Sapkota, Dipak, Ahmed, Israa A. H., Johannessen, Anne Ch, Costea, Daniela Elena
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container_end_page 419
container_issue 6
container_start_page 410
container_title Journal of oral pathology & medicine
container_volume 44
creator Osman, Tarig A.
Parajuli, Himalaya
Sapkota, Dipak
Ahmed, Israa A. H.
Johannessen, Anne Ch
Costea, Daniela Elena
description Background Although several markers have been used for enrichment of cells with stem cell‐like properties in oral squamous cell carcinoma (OSCC), isolation of a pure subpopulation is still a challenging task. Normal oral and esophageal keratinocyte stem cells have been previously isolated using the low‐affinity nerve growth factor receptor p75NTR. Objective To investigate the potential of p75NTR as a marker for identification and isolation of oral cancer cells with stem cell‐like properties. Methods Subpopulations of cells with high or low expression of p75NTR were sorted from OSCC‐derived cells and compared for sphere/colony formation, in vivo tumor formation ability, expression of stem cell‐related molecules, cell cycle distribution and drug resistance. Results p75NTRHigh cells exhibited statistically significant higher stem cell properties than p75NTRLow cells in all assays performed. Nevertheless, p75NTRLow subpopulation did also exhibit some stem cell features, but to a lesser extent. Propagation of p75NTRLow cells for several passages in culture showed that the expression of p75NTR could rise spontaneously. This finding was also supported by the similar expression of p75NTR by the xenografts generated by both subpopulations in NOD\SCID IL2Rgnullmice. Conclusion p75NTR can be used for isolating a subpopulation enriched for cells with stem cell‐like properties in OSCC. De novo generation of p75NTRHigh cells from p75NTRLow cells suggests either that there is another subpopulation with stem cell features within the p75NTRLow cells, or that the p75NTRLow cells can dedifferentiate due to a contextually regulated equilibrium between stem cell‐like cells and transit‐amplifying neoplastic progenitors.
doi_str_mv 10.1111/jop.12251
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H. ; Johannessen, Anne Ch ; Costea, Daniela Elena</creator><creatorcontrib>Osman, Tarig A. ; Parajuli, Himalaya ; Sapkota, Dipak ; Ahmed, Israa A. H. ; Johannessen, Anne Ch ; Costea, Daniela Elena</creatorcontrib><description>Background Although several markers have been used for enrichment of cells with stem cell‐like properties in oral squamous cell carcinoma (OSCC), isolation of a pure subpopulation is still a challenging task. Normal oral and esophageal keratinocyte stem cells have been previously isolated using the low‐affinity nerve growth factor receptor p75NTR. Objective To investigate the potential of p75NTR as a marker for identification and isolation of oral cancer cells with stem cell‐like properties. Methods Subpopulations of cells with high or low expression of p75NTR were sorted from OSCC‐derived cells and compared for sphere/colony formation, in vivo tumor formation ability, expression of stem cell‐related molecules, cell cycle distribution and drug resistance. Results p75NTRHigh cells exhibited statistically significant higher stem cell properties than p75NTRLow cells in all assays performed. Nevertheless, p75NTRLow subpopulation did also exhibit some stem cell features, but to a lesser extent. Propagation of p75NTRLow cells for several passages in culture showed that the expression of p75NTR could rise spontaneously. This finding was also supported by the similar expression of p75NTR by the xenografts generated by both subpopulations in NOD\SCID IL2Rgnullmice. Conclusion p75NTR can be used for isolating a subpopulation enriched for cells with stem cell‐like properties in OSCC. De novo generation of p75NTRHigh cells from p75NTRLow cells suggests either that there is another subpopulation with stem cell features within the p75NTRLow cells, or that the p75NTRLow cells can dedifferentiate due to a contextually regulated equilibrium between stem cell‐like cells and transit‐amplifying neoplastic progenitors.</description><identifier>ISSN: 0904-2512</identifier><identifier>EISSN: 1600-0714</identifier><identifier>DOI: 10.1111/jop.12251</identifier><identifier>PMID: 25212757</identifier><language>eng</language><publisher>Denmark: Blackwell Publishing Ltd</publisher><subject>Animals ; Biomarkers, Tumor - metabolism ; cancer stem cell ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Cell Cycle - physiology ; Cell Line, Tumor ; Dentistry ; Head and Neck Neoplasms - metabolism ; Head and Neck Neoplasms - pathology ; Heterografts ; Humans ; Immunohistochemistry - methods ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Mouth Neoplasms - metabolism ; Mouth Neoplasms - pathology ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - pathology ; Nerve Tissue Proteins - metabolism ; oral squamous cell carcinoma ; p75NTR ; plasticity ; Receptors, Nerve Growth Factor - metabolism ; Squamous Cell Carcinoma of Head and Neck ; stochastic stem cell ; tumor heterogeneity</subject><ispartof>Journal of oral pathology &amp; medicine, 2015-07, Vol.44 (6), p.410-419</ispartof><rights>2014 The Authors. Published by John Wiley &amp; Sons Ltd</rights><rights>2014 The Authors. Journal of Oral Pathology &amp; Medicine Published by John Wiley &amp; Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjop.12251$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjop.12251$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25212757$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Osman, Tarig A.</creatorcontrib><creatorcontrib>Parajuli, Himalaya</creatorcontrib><creatorcontrib>Sapkota, Dipak</creatorcontrib><creatorcontrib>Ahmed, Israa A. H.</creatorcontrib><creatorcontrib>Johannessen, Anne Ch</creatorcontrib><creatorcontrib>Costea, Daniela Elena</creatorcontrib><title>The low-affinity nerve growth factor receptor p75NTR identifies a transient stem cell-like state in oral squamous cell carcinoma cells</title><title>Journal of oral pathology &amp; medicine</title><addtitle>J Oral Pathol Med</addtitle><description>Background Although several markers have been used for enrichment of cells with stem cell‐like properties in oral squamous cell carcinoma (OSCC), isolation of a pure subpopulation is still a challenging task. Normal oral and esophageal keratinocyte stem cells have been previously isolated using the low‐affinity nerve growth factor receptor p75NTR. Objective To investigate the potential of p75NTR as a marker for identification and isolation of oral cancer cells with stem cell‐like properties. Methods Subpopulations of cells with high or low expression of p75NTR were sorted from OSCC‐derived cells and compared for sphere/colony formation, in vivo tumor formation ability, expression of stem cell‐related molecules, cell cycle distribution and drug resistance. Results p75NTRHigh cells exhibited statistically significant higher stem cell properties than p75NTRLow cells in all assays performed. Nevertheless, p75NTRLow subpopulation did also exhibit some stem cell features, but to a lesser extent. Propagation of p75NTRLow cells for several passages in culture showed that the expression of p75NTR could rise spontaneously. This finding was also supported by the similar expression of p75NTR by the xenografts generated by both subpopulations in NOD\SCID IL2Rgnullmice. Conclusion p75NTR can be used for isolating a subpopulation enriched for cells with stem cell‐like properties in OSCC. De novo generation of p75NTRHigh cells from p75NTRLow cells suggests either that there is another subpopulation with stem cell features within the p75NTRLow cells, or that the p75NTRLow cells can dedifferentiate due to a contextually regulated equilibrium between stem cell‐like cells and transit‐amplifying neoplastic progenitors.</description><subject>Animals</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>cancer stem cell</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell Cycle - physiology</subject><subject>Cell Line, Tumor</subject><subject>Dentistry</subject><subject>Head and Neck Neoplasms - metabolism</subject><subject>Head and Neck Neoplasms - pathology</subject><subject>Heterografts</subject><subject>Humans</subject><subject>Immunohistochemistry - methods</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Mouth Neoplasms - metabolism</subject><subject>Mouth Neoplasms - pathology</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>oral squamous cell carcinoma</subject><subject>p75NTR</subject><subject>plasticity</subject><subject>Receptors, Nerve Growth Factor - metabolism</subject><subject>Squamous Cell Carcinoma of Head and Neck</subject><subject>stochastic stem cell</subject><subject>tumor heterogeneity</subject><issn>0904-2512</issn><issn>1600-0714</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNo9kU1PGzEQhq2qiKSUQ_9A5WMvSzzetb17rFCTgqKAShBHy1nPNob9wt405A_0d-MkwFw8H89rjeYl5BuwC4gxeez6C-BcwCcyBslYwhRkn8mYFSxLYpuPyJcQHhkDlWZwSkZccOBKqDH5v1wjrbttYqrKtW7Y0Rb9P6R_fbcd1rQy5dB56rHEfp_0SiyWf6iz2A6uchiooYM3bXCxQcOADS2xrpPaPWEszYDUtbTzpqbheWOabhMOAC2NL13bNeZQhq_kpDJ1wPO394zcT38tL38n85vZ1eXPeeLSIoMk5yKVTMlcCsiktLliJitW1jDJbblCWyhjVxkTFaAsc2mtzFlqixwKgRJEekZ-HP_tffe8wTDoxoX9BqbFuJsGWaQqwjmP6Pc3dLNq0Oreu8b4nX6_XQQmR2Dratx9zIHpvSk6mqIPpujrm9tDEhXJUeHipV4-FMY_aalSJfTDYqZvYX43zWZTfZe-Ahvljo8</recordid><startdate>201507</startdate><enddate>201507</enddate><creator>Osman, Tarig A.</creator><creator>Parajuli, Himalaya</creator><creator>Sapkota, Dipak</creator><creator>Ahmed, Israa A. H.</creator><creator>Johannessen, Anne Ch</creator><creator>Costea, Daniela Elena</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201507</creationdate><title>The low-affinity nerve growth factor receptor p75NTR identifies a transient stem cell-like state in oral squamous cell carcinoma cells</title><author>Osman, Tarig A. ; Parajuli, Himalaya ; Sapkota, Dipak ; Ahmed, Israa A. H. ; Johannessen, Anne Ch ; Costea, Daniela Elena</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-i3941-825360768651466d870a49bda062dcbed97adb405f1e6c86dd6803d98195e6153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>cancer stem cell</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Cell Cycle - physiology</topic><topic>Cell Line, Tumor</topic><topic>Dentistry</topic><topic>Head and Neck Neoplasms - metabolism</topic><topic>Head and Neck Neoplasms - pathology</topic><topic>Heterografts</topic><topic>Humans</topic><topic>Immunohistochemistry - methods</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Mouth Neoplasms - metabolism</topic><topic>Mouth Neoplasms - pathology</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>oral squamous cell carcinoma</topic><topic>p75NTR</topic><topic>plasticity</topic><topic>Receptors, Nerve Growth Factor - metabolism</topic><topic>Squamous Cell Carcinoma of Head and Neck</topic><topic>stochastic stem cell</topic><topic>tumor heterogeneity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Osman, Tarig A.</creatorcontrib><creatorcontrib>Parajuli, Himalaya</creatorcontrib><creatorcontrib>Sapkota, Dipak</creatorcontrib><creatorcontrib>Ahmed, Israa A. H.</creatorcontrib><creatorcontrib>Johannessen, Anne Ch</creatorcontrib><creatorcontrib>Costea, Daniela Elena</creatorcontrib><collection>Istex</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of oral pathology &amp; medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Osman, Tarig A.</au><au>Parajuli, Himalaya</au><au>Sapkota, Dipak</au><au>Ahmed, Israa A. H.</au><au>Johannessen, Anne Ch</au><au>Costea, Daniela Elena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The low-affinity nerve growth factor receptor p75NTR identifies a transient stem cell-like state in oral squamous cell carcinoma cells</atitle><jtitle>Journal of oral pathology &amp; medicine</jtitle><addtitle>J Oral Pathol Med</addtitle><date>2015-07</date><risdate>2015</risdate><volume>44</volume><issue>6</issue><spage>410</spage><epage>419</epage><pages>410-419</pages><issn>0904-2512</issn><eissn>1600-0714</eissn><abstract>Background Although several markers have been used for enrichment of cells with stem cell‐like properties in oral squamous cell carcinoma (OSCC), isolation of a pure subpopulation is still a challenging task. Normal oral and esophageal keratinocyte stem cells have been previously isolated using the low‐affinity nerve growth factor receptor p75NTR. Objective To investigate the potential of p75NTR as a marker for identification and isolation of oral cancer cells with stem cell‐like properties. Methods Subpopulations of cells with high or low expression of p75NTR were sorted from OSCC‐derived cells and compared for sphere/colony formation, in vivo tumor formation ability, expression of stem cell‐related molecules, cell cycle distribution and drug resistance. Results p75NTRHigh cells exhibited statistically significant higher stem cell properties than p75NTRLow cells in all assays performed. Nevertheless, p75NTRLow subpopulation did also exhibit some stem cell features, but to a lesser extent. Propagation of p75NTRLow cells for several passages in culture showed that the expression of p75NTR could rise spontaneously. This finding was also supported by the similar expression of p75NTR by the xenografts generated by both subpopulations in NOD\SCID IL2Rgnullmice. Conclusion p75NTR can be used for isolating a subpopulation enriched for cells with stem cell‐like properties in OSCC. De novo generation of p75NTRHigh cells from p75NTRLow cells suggests either that there is another subpopulation with stem cell features within the p75NTRLow cells, or that the p75NTRLow cells can dedifferentiate due to a contextually regulated equilibrium between stem cell‐like cells and transit‐amplifying neoplastic progenitors.</abstract><cop>Denmark</cop><pub>Blackwell Publishing Ltd</pub><pmid>25212757</pmid><doi>10.1111/jop.12251</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Biomarkers, Tumor - metabolism
cancer stem cell
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
Cell Cycle - physiology
Cell Line, Tumor
Dentistry
Head and Neck Neoplasms - metabolism
Head and Neck Neoplasms - pathology
Heterografts
Humans
Immunohistochemistry - methods
Mice
Mice, Inbred NOD
Mice, SCID
Mouth Neoplasms - metabolism
Mouth Neoplasms - pathology
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Nerve Tissue Proteins - metabolism
oral squamous cell carcinoma
p75NTR
plasticity
Receptors, Nerve Growth Factor - metabolism
Squamous Cell Carcinoma of Head and Neck
stochastic stem cell
tumor heterogeneity
title The low-affinity nerve growth factor receptor p75NTR identifies a transient stem cell-like state in oral squamous cell carcinoma cells
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