Spheroid-based 3-dimensional culture models: Gene expression and functionality in head and neck cancer
In the present study a panel of 12 head and neck cancer (HNSCC) cell lines were tested for spheroid formation. Since the size and morphology of spheroids is dependent on both cell adhesion and proliferation in the 3-dimensional (3D) context, morphology of HNSCC spheroids was related to expression of...
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| Veröffentlicht in: | Oncology reports 2016-04, Vol.35 (4), p.2431-2440 |
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| creator | SCHMIDT, MARIANNE SCHOLZ, CLAUS-JUERGEN POLEDNIK, CHRISTINE ROLLER, JEANETTE |
| description | In the present study a panel of 12 head and neck cancer (HNSCC) cell lines were tested for spheroid formation. Since the size and morphology of spheroids is dependent on both cell adhesion and proliferation in the 3-dimensional (3D) context, morphology of HNSCC spheroids was related to expression of E-cadherin and the proliferation marker Ki67. In HNSCC cell lines the formation of tight regular spheroids was dependent on distinct E-cadherin expression levels in monolayer cultures, usually resulting in upregulation following aggregation into 3D structures. Cell lines expressing only low levels of E-cadherin in monolayers produced only loose cell clusters, frequently decreasing E-cadherin expression further upon aggregation. In these cell lines no epidermal growth factor receptor (EGFR) upregulation occurred and proliferation generally decreased in spheroids/aggregates independent of E-cadherin expression. In a second approach a global gene expression analysis of the larynx carcinoma cell line HLaC78 monolayer and the corresponding spheroids was performed. A global upregulation of gene expression in HLaC78 spheroids was related to genes involved in cell adhesion, cell junctions and cytochrome P450-mediated metabolism of xenobiotics. Downregulation was associated with genes controlling cell cycle, DNA-replication and DNA mismatch repair. Analyzing the expression of selected genes of each functional group in monolayer and spheroid cultures of all 12 cell lines revealed evidence for common gene expression shifts in genes controlling cell junctions, cell adhesion, cell cycle and DNA replication as well as genes involved in the cytochrome P450-mediated metabolism of xenobiotics. |
| doi_str_mv | 10.3892/or.2016.4581 |
| format | Article |
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Since the size and morphology of spheroids is dependent on both cell adhesion and proliferation in the 3-dimensional (3D) context, morphology of HNSCC spheroids was related to expression of E-cadherin and the proliferation marker Ki67. In HNSCC cell lines the formation of tight regular spheroids was dependent on distinct E-cadherin expression levels in monolayer cultures, usually resulting in upregulation following aggregation into 3D structures. Cell lines expressing only low levels of E-cadherin in monolayers produced only loose cell clusters, frequently decreasing E-cadherin expression further upon aggregation. In these cell lines no epidermal growth factor receptor (EGFR) upregulation occurred and proliferation generally decreased in spheroids/aggregates independent of E-cadherin expression. In a second approach a global gene expression analysis of the larynx carcinoma cell line HLaC78 monolayer and the corresponding spheroids was performed. A global upregulation of gene expression in HLaC78 spheroids was related to genes involved in cell adhesion, cell junctions and cytochrome P450-mediated metabolism of xenobiotics. Downregulation was associated with genes controlling cell cycle, DNA-replication and DNA mismatch repair. Analyzing the expression of selected genes of each functional group in monolayer and spheroid cultures of all 12 cell lines revealed evidence for common gene expression shifts in genes controlling cell junctions, cell adhesion, cell cycle and DNA replication as well as genes involved in the cytochrome P450-mediated metabolism of xenobiotics.</description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or.2016.4581</identifier><identifier>PMID: 26797047</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>3D culture ; Antigens ; Cadherins - genetics ; cancer ; carcinoma ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - pathology ; Cell Adhesion ; Cell adhesion & migration ; Cell Culture Techniques - methods ; Cell cycle ; Cell Line, Tumor ; Cell Proliferation ; Cell Size ; Cellular proteins ; Cytochrome ; Deoxyribonucleic acid ; Development and progression ; DNA ; E coli ; E-cadherin ; Extracellular matrix ; Gene Expression ; Gene Expression Profiling - methods ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Genetic aspects ; Head & neck cancer ; head and neck ; Head and neck cancer ; Head and Neck Neoplasms - genetics ; Head and Neck Neoplasms - pathology ; Health aspects ; HNSCC ; Humans ; in vitro ; Ki-67 Antigen - genetics ; Laryngeal Neoplasms - metabolism ; Laryngeal Neoplasms - pathology ; Medical prognosis ; microarray ; Morphology ; Oligonucleotide Array Sequence Analysis - methods ; Polypeptides ; proliferation ; Properties ; Proteins ; Spheroids, Cellular - metabolism ; Spheroids, Cellular - pathology ; Squamous Cell Carcinoma of Head and Neck ; Values</subject><ispartof>Oncology reports, 2016-04, Vol.35 (4), p.2431-2440</ispartof><rights>Copyright © 2016, Spandidos Publications</rights><rights>COPYRIGHT 2016 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-967ba971b77351762a79fca070657487625d313ef17ac3f44aa791da720c51063</citedby><cites>FETCH-LOGICAL-c486t-967ba971b77351762a79fca070657487625d313ef17ac3f44aa791da720c51063</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26797047$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SCHMIDT, MARIANNE</creatorcontrib><creatorcontrib>SCHOLZ, CLAUS-JUERGEN</creatorcontrib><creatorcontrib>POLEDNIK, CHRISTINE</creatorcontrib><creatorcontrib>ROLLER, JEANETTE</creatorcontrib><title>Spheroid-based 3-dimensional culture models: Gene expression and functionality in head and neck cancer</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description>In the present study a panel of 12 head and neck cancer (HNSCC) cell lines were tested for spheroid formation. Since the size and morphology of spheroids is dependent on both cell adhesion and proliferation in the 3-dimensional (3D) context, morphology of HNSCC spheroids was related to expression of E-cadherin and the proliferation marker Ki67. In HNSCC cell lines the formation of tight regular spheroids was dependent on distinct E-cadherin expression levels in monolayer cultures, usually resulting in upregulation following aggregation into 3D structures. Cell lines expressing only low levels of E-cadherin in monolayers produced only loose cell clusters, frequently decreasing E-cadherin expression further upon aggregation. In these cell lines no epidermal growth factor receptor (EGFR) upregulation occurred and proliferation generally decreased in spheroids/aggregates independent of E-cadherin expression. In a second approach a global gene expression analysis of the larynx carcinoma cell line HLaC78 monolayer and the corresponding spheroids was performed. A global upregulation of gene expression in HLaC78 spheroids was related to genes involved in cell adhesion, cell junctions and cytochrome P450-mediated metabolism of xenobiotics. Downregulation was associated with genes controlling cell cycle, DNA-replication and DNA mismatch repair. Analyzing the expression of selected genes of each functional group in monolayer and spheroid cultures of all 12 cell lines revealed evidence for common gene expression shifts in genes controlling cell junctions, cell adhesion, cell cycle and DNA replication as well as genes involved in the cytochrome P450-mediated metabolism of xenobiotics.</description><subject>3D culture</subject><subject>Antigens</subject><subject>Cadherins - genetics</subject><subject>cancer</subject><subject>carcinoma</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell Adhesion</subject><subject>Cell adhesion & migration</subject><subject>Cell Culture Techniques - methods</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cell Size</subject><subject>Cellular proteins</subject><subject>Cytochrome</subject><subject>Deoxyribonucleic acid</subject><subject>Development and progression</subject><subject>DNA</subject><subject>E coli</subject><subject>E-cadherin</subject><subject>Extracellular matrix</subject><subject>Gene Expression</subject><subject>Gene Expression Profiling - methods</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Regulatory Networks</subject><subject>Genetic aspects</subject><subject>Head & neck cancer</subject><subject>head and neck</subject><subject>Head and neck cancer</subject><subject>Head and Neck Neoplasms - genetics</subject><subject>Head and Neck Neoplasms - pathology</subject><subject>Health aspects</subject><subject>HNSCC</subject><subject>Humans</subject><subject>in vitro</subject><subject>Ki-67 Antigen - genetics</subject><subject>Laryngeal Neoplasms - metabolism</subject><subject>Laryngeal Neoplasms - pathology</subject><subject>Medical prognosis</subject><subject>microarray</subject><subject>Morphology</subject><subject>Oligonucleotide Array Sequence Analysis - methods</subject><subject>Polypeptides</subject><subject>proliferation</subject><subject>Properties</subject><subject>Proteins</subject><subject>Spheroids, Cellular - metabolism</subject><subject>Spheroids, Cellular - pathology</subject><subject>Squamous Cell Carcinoma of Head and Neck</subject><subject>Values</subject><issn>1021-335X</issn><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpt0ktvFSEYBmBiNPaiO9eGxMR04Ry5zQDdNY1WkyYu1MQd4cA3HuoMjDCT2H8vc1pbawwLCDxcXxB6QcmGK83eprxhhHYb0Sr6CB1SqWnDBKePa5sw2nDefjtAR6VcEcIk6fRTdMA6qSUR8hD1n6cd5BR8s7UFPOaNDyPEElK0A3bLMC8Z8Jg8DOUUX0AEDL-mDGUV2EaP-yW6ec_DfI1DxDuwfj8Swf3AzkYH-Rl60tuhwPPb-hh9ff_uy_mH5vLTxcfzs8vGCdXNje7k1mpJt1LylsqOWal7Z0k9diuFqh2t55RDT6V1vBfCVkC9lYy4lpKOH6OTm3WnnH4uUGYzhuJgGGyEtBRDpdRKCaJZpa_-oVdpyfUaVWnOOqWF7O7VdzuACbFPc7ZuXdScCaEVV4qSqjb_UbV4GINLEfpQ-x9MeP3XhPpiw7wraVjWhywP4Zsb6HIqJUNvphxGm68NJWbN36Rs1vzNmn_lL28vtWxH8Hf4T-D3G5epRhR8Kncm5Ya3DRH738N_A9-Gs_0</recordid><startdate>20160401</startdate><enddate>20160401</enddate><creator>SCHMIDT, MARIANNE</creator><creator>SCHOLZ, CLAUS-JUERGEN</creator><creator>POLEDNIK, CHRISTINE</creator><creator>ROLLER, JEANETTE</creator><general>D.A. 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genetics</topic><topic>cancer</topic><topic>carcinoma</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Cell Adhesion</topic><topic>Cell adhesion & migration</topic><topic>Cell Culture Techniques - methods</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cell Size</topic><topic>Cellular proteins</topic><topic>Cytochrome</topic><topic>Deoxyribonucleic acid</topic><topic>Development and progression</topic><topic>DNA</topic><topic>E coli</topic><topic>E-cadherin</topic><topic>Extracellular matrix</topic><topic>Gene Expression</topic><topic>Gene Expression Profiling - methods</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Regulatory Networks</topic><topic>Genetic aspects</topic><topic>Head & neck cancer</topic><topic>head and neck</topic><topic>Head and neck cancer</topic><topic>Head and Neck Neoplasms - genetics</topic><topic>Head and Neck Neoplasms - pathology</topic><topic>Health aspects</topic><topic>HNSCC</topic><topic>Humans</topic><topic>in vitro</topic><topic>Ki-67 Antigen - genetics</topic><topic>Laryngeal Neoplasms - metabolism</topic><topic>Laryngeal Neoplasms - pathology</topic><topic>Medical prognosis</topic><topic>microarray</topic><topic>Morphology</topic><topic>Oligonucleotide Array Sequence Analysis - methods</topic><topic>Polypeptides</topic><topic>proliferation</topic><topic>Properties</topic><topic>Proteins</topic><topic>Spheroids, Cellular - metabolism</topic><topic>Spheroids, Cellular - pathology</topic><topic>Squamous Cell Carcinoma of Head and Neck</topic><topic>Values</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SCHMIDT, MARIANNE</creatorcontrib><creatorcontrib>SCHOLZ, CLAUS-JUERGEN</creatorcontrib><creatorcontrib>POLEDNIK, CHRISTINE</creatorcontrib><creatorcontrib>ROLLER, JEANETTE</creatorcontrib><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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</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><jtitle>Oncology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SCHMIDT, MARIANNE</au><au>SCHOLZ, CLAUS-JUERGEN</au><au>POLEDNIK, CHRISTINE</au><au>ROLLER, JEANETTE</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Spheroid-based 3-dimensional culture models: Gene expression and functionality in head and neck cancer</atitle><jtitle>Oncology reports</jtitle><addtitle>Oncol Rep</addtitle><date>2016-04-01</date><risdate>2016</risdate><volume>35</volume><issue>4</issue><spage>2431</spage><epage>2440</epage><pages>2431-2440</pages><issn>1021-335X</issn><eissn>1791-2431</eissn><abstract>In the present study a panel of 12 head and neck cancer (HNSCC) cell lines were tested for spheroid formation. Since the size and morphology of spheroids is dependent on both cell adhesion and proliferation in the 3-dimensional (3D) context, morphology of HNSCC spheroids was related to expression of E-cadherin and the proliferation marker Ki67. In HNSCC cell lines the formation of tight regular spheroids was dependent on distinct E-cadherin expression levels in monolayer cultures, usually resulting in upregulation following aggregation into 3D structures. Cell lines expressing only low levels of E-cadherin in monolayers produced only loose cell clusters, frequently decreasing E-cadherin expression further upon aggregation. In these cell lines no epidermal growth factor receptor (EGFR) upregulation occurred and proliferation generally decreased in spheroids/aggregates independent of E-cadherin expression. In a second approach a global gene expression analysis of the larynx carcinoma cell line HLaC78 monolayer and the corresponding spheroids was performed. A global upregulation of gene expression in HLaC78 spheroids was related to genes involved in cell adhesion, cell junctions and cytochrome P450-mediated metabolism of xenobiotics. Downregulation was associated with genes controlling cell cycle, DNA-replication and DNA mismatch repair. Analyzing the expression of selected genes of each functional group in monolayer and spheroid cultures of all 12 cell lines revealed evidence for common gene expression shifts in genes controlling cell junctions, cell adhesion, cell cycle and DNA replication as well as genes involved in the cytochrome P450-mediated metabolism of xenobiotics.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>26797047</pmid><doi>10.3892/or.2016.4581</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Oncology reports, 2016-04, Vol.35 (4), p.2431-2440 |
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| subjects | 3D culture Antigens Cadherins - genetics cancer carcinoma Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - pathology Cell Adhesion Cell adhesion & migration Cell Culture Techniques - methods Cell cycle Cell Line, Tumor Cell Proliferation Cell Size Cellular proteins Cytochrome Deoxyribonucleic acid Development and progression DNA E coli E-cadherin Extracellular matrix Gene Expression Gene Expression Profiling - methods Gene Expression Regulation, Neoplastic Gene Regulatory Networks Genetic aspects Head & neck cancer head and neck Head and neck cancer Head and Neck Neoplasms - genetics Head and Neck Neoplasms - pathology Health aspects HNSCC Humans in vitro Ki-67 Antigen - genetics Laryngeal Neoplasms - metabolism Laryngeal Neoplasms - pathology Medical prognosis microarray Morphology Oligonucleotide Array Sequence Analysis - methods Polypeptides proliferation Properties Proteins Spheroids, Cellular - metabolism Spheroids, Cellular - pathology Squamous Cell Carcinoma of Head and Neck Values |
| title | Spheroid-based 3-dimensional culture models: Gene expression and functionality in head and neck cancer |
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