Expression of Proinflammatory and Proangiogenic Cytokines in Patients with Head and Neck Cancer
Altered immune, inflammatory, and angiogenesis responses are observed in patients with head and neck squamous cell carcinoma (HNSCC), and many of these responses have been linked with aggressive malignant behavior and a decrease in prognosis. In this study, we examined the hypothesis that HNSCC cell...
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| Veröffentlicht in: | Clinical cancer research 1999-06, Vol.5 (6), p.1369-1379 |
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| creator | ZHONG CHEN MALHOTRA, P. S MCCULLAGH, L MOUSA, S QUEZADO, M HERSCHER, L. L VAN WAES, C THOMAS, G. R ONDREY, F. G DUFFEY, D. C SMITH, C. W ENAMORADO, I YEH, N. T KROOG, G. S RUDY, S |
| description | Altered immune, inflammatory, and angiogenesis responses are observed in patients with head and neck squamous cell carcinoma
(HNSCC), and many of these responses have been linked with aggressive malignant behavior and a decrease in prognosis. In this
study, we examined the hypothesis that HNSCC cells produce cytokines that regulate immune, inflammatory, and angiogenesis
responses. We identified important regulatory cytokines in supernatants of well-defined and freshly cultured HNSCC cell lines
by ELISA and determined whether these cytokines are detected in tumor cell lines and tissue specimens by immunohistochemistry.
The serum concentration of the cytokines and cytokine-dependent acute phase inflammatory responses ( i.e. , fibrinogen, C-reactive protein, and erythrocyte sedimentation rate) from patients with HNSCC was determined, and the potential
relationship of serum cytokine levels to tumor volume was analyzed. Cytokines interleukin (IL)-1α, IL-6, IL-8, granulocyte-macrophage
colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor were detected
in similar concentration ranges in the supernatants of a panel of established University of Michigan squamous cell carcinoma
(UM-SCC) cell lines and supernatants of freshly isolated primary HNSCC cultures. Evidence for the expression of IL-1α, IL-6,
IL-8, granulocyte-macrophage colony-stimulating factor, and VEGF in HNSCC cells within tumor specimens in situ was obtained by immunohistochemistry. In a prospective comparison of the cytokine level and cytokine-inducible acute-phase
proteins in serum, we report that cytokines IL-6, IL-8, and VEGF were detected at higher concentrations in the serum of patients
with HNSCC compared with patients with laryngeal papilloma or age-matched control subjects (at P < 0.05). The serum concentrations of IL-8 and VEGF were found to be weakly correlated with large primary tumor volume (R 2 = 0.2 and 0.4, respectively). Elevated IL-1- and IL-6-inducible acute-phase responses were also detected in cancer patients
but not in patients with papilloma or control subjects (at P < 0.05). We therefore conclude that cytokines important in proinflammatory and proangiogenic responses are detectable in
cell lines, tissue specimens, and serum from patients with HNSCC. These cytokines may increase the pathogenicity of HNSCC
and prove useful as biomarkers or targets for therapy. |
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(HNSCC), and many of these responses have been linked with aggressive malignant behavior and a decrease in prognosis. In this
study, we examined the hypothesis that HNSCC cells produce cytokines that regulate immune, inflammatory, and angiogenesis
responses. We identified important regulatory cytokines in supernatants of well-defined and freshly cultured HNSCC cell lines
by ELISA and determined whether these cytokines are detected in tumor cell lines and tissue specimens by immunohistochemistry.
The serum concentration of the cytokines and cytokine-dependent acute phase inflammatory responses ( i.e. , fibrinogen, C-reactive protein, and erythrocyte sedimentation rate) from patients with HNSCC was determined, and the potential
relationship of serum cytokine levels to tumor volume was analyzed. Cytokines interleukin (IL)-1α, IL-6, IL-8, granulocyte-macrophage
colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor were detected
in similar concentration ranges in the supernatants of a panel of established University of Michigan squamous cell carcinoma
(UM-SCC) cell lines and supernatants of freshly isolated primary HNSCC cultures. Evidence for the expression of IL-1α, IL-6,
IL-8, granulocyte-macrophage colony-stimulating factor, and VEGF in HNSCC cells within tumor specimens in situ was obtained by immunohistochemistry. In a prospective comparison of the cytokine level and cytokine-inducible acute-phase
proteins in serum, we report that cytokines IL-6, IL-8, and VEGF were detected at higher concentrations in the serum of patients
with HNSCC compared with patients with laryngeal papilloma or age-matched control subjects (at P < 0.05). The serum concentrations of IL-8 and VEGF were found to be weakly correlated with large primary tumor volume (R 2 = 0.2 and 0.4, respectively). Elevated IL-1- and IL-6-inducible acute-phase responses were also detected in cancer patients
but not in patients with papilloma or control subjects (at P < 0.05). We therefore conclude that cytokines important in proinflammatory and proangiogenic responses are detectable in
cell lines, tissue specimens, and serum from patients with HNSCC. These cytokines may increase the pathogenicity of HNSCC
and prove useful as biomarkers or targets for therapy.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 10389921</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Acute-Phase Reaction - immunology ; Adult ; Aged ; Biological and medical sciences ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - secretion ; Cytokines - metabolism ; Cytokines - secretion ; Endothelial Growth Factors - metabolism ; Endothelial Growth Factors - secretion ; Enzyme-Linked Immunosorbent Assay ; Female ; Fibroblast Growth Factor 2 - metabolism ; Fibroblast Growth Factor 2 - secretion ; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism ; Granulocyte-Macrophage Colony-Stimulating Factor - secretion ; Head and Neck Neoplasms - metabolism ; Head and Neck Neoplasms - secretion ; Humans ; Immunohistochemistry ; Inflammation - metabolism ; Interleukin-1 - metabolism ; Interleukin-1 - secretion ; Interleukin-6 - metabolism ; Interleukin-6 - secretion ; Interleukin-8 - metabolism ; Interleukin-8 - secretion ; Lymphokines - metabolism ; Lymphokines - secretion ; Male ; Medical sciences ; Middle Aged ; Otorhinolaryngology (head neck, general aspects and miscellaneous) ; Otorhinolaryngology. Stomatology ; Prospective Studies ; Tumor Cells, Cultured ; Tumors ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors</subject><ispartof>Clinical cancer research, 1999-06, Vol.5 (6), p.1369-1379</ispartof><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1833217$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10389921$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ZHONG CHEN</creatorcontrib><creatorcontrib>MALHOTRA, P. S</creatorcontrib><creatorcontrib>MCCULLAGH, L</creatorcontrib><creatorcontrib>MOUSA, S</creatorcontrib><creatorcontrib>QUEZADO, M</creatorcontrib><creatorcontrib>HERSCHER, L. L</creatorcontrib><creatorcontrib>VAN WAES, C</creatorcontrib><creatorcontrib>THOMAS, G. R</creatorcontrib><creatorcontrib>ONDREY, F. G</creatorcontrib><creatorcontrib>DUFFEY, D. C</creatorcontrib><creatorcontrib>SMITH, C. W</creatorcontrib><creatorcontrib>ENAMORADO, I</creatorcontrib><creatorcontrib>YEH, N. T</creatorcontrib><creatorcontrib>KROOG, G. S</creatorcontrib><creatorcontrib>RUDY, S</creatorcontrib><title>Expression of Proinflammatory and Proangiogenic Cytokines in Patients with Head and Neck Cancer</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Altered immune, inflammatory, and angiogenesis responses are observed in patients with head and neck squamous cell carcinoma
(HNSCC), and many of these responses have been linked with aggressive malignant behavior and a decrease in prognosis. In this
study, we examined the hypothesis that HNSCC cells produce cytokines that regulate immune, inflammatory, and angiogenesis
responses. We identified important regulatory cytokines in supernatants of well-defined and freshly cultured HNSCC cell lines
by ELISA and determined whether these cytokines are detected in tumor cell lines and tissue specimens by immunohistochemistry.
The serum concentration of the cytokines and cytokine-dependent acute phase inflammatory responses ( i.e. , fibrinogen, C-reactive protein, and erythrocyte sedimentation rate) from patients with HNSCC was determined, and the potential
relationship of serum cytokine levels to tumor volume was analyzed. Cytokines interleukin (IL)-1α, IL-6, IL-8, granulocyte-macrophage
colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor were detected
in similar concentration ranges in the supernatants of a panel of established University of Michigan squamous cell carcinoma
(UM-SCC) cell lines and supernatants of freshly isolated primary HNSCC cultures. Evidence for the expression of IL-1α, IL-6,
IL-8, granulocyte-macrophage colony-stimulating factor, and VEGF in HNSCC cells within tumor specimens in situ was obtained by immunohistochemistry. In a prospective comparison of the cytokine level and cytokine-inducible acute-phase
proteins in serum, we report that cytokines IL-6, IL-8, and VEGF were detected at higher concentrations in the serum of patients
with HNSCC compared with patients with laryngeal papilloma or age-matched control subjects (at P < 0.05). The serum concentrations of IL-8 and VEGF were found to be weakly correlated with large primary tumor volume (R 2 = 0.2 and 0.4, respectively). Elevated IL-1- and IL-6-inducible acute-phase responses were also detected in cancer patients
but not in patients with papilloma or control subjects (at P < 0.05). We therefore conclude that cytokines important in proinflammatory and proangiogenic responses are detectable in
cell lines, tissue specimens, and serum from patients with HNSCC. These cytokines may increase the pathogenicity of HNSCC
and prove useful as biomarkers or targets for therapy.</description><subject>Acute-Phase Reaction - immunology</subject><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - secretion</subject><subject>Cytokines - metabolism</subject><subject>Cytokines - secretion</subject><subject>Endothelial Growth Factors - metabolism</subject><subject>Endothelial Growth Factors - secretion</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Fibroblast Growth Factor 2 - metabolism</subject><subject>Fibroblast Growth Factor 2 - secretion</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - metabolism</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - secretion</subject><subject>Head and Neck Neoplasms - metabolism</subject><subject>Head and Neck Neoplasms - secretion</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Inflammation - metabolism</subject><subject>Interleukin-1 - metabolism</subject><subject>Interleukin-1 - secretion</subject><subject>Interleukin-6 - metabolism</subject><subject>Interleukin-6 - secretion</subject><subject>Interleukin-8 - metabolism</subject><subject>Interleukin-8 - secretion</subject><subject>Lymphokines - metabolism</subject><subject>Lymphokines - secretion</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Otorhinolaryngology (head neck, general aspects and miscellaneous)</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Prospective Studies</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><subject>Vascular Endothelial Growth Factor A</subject><subject>Vascular Endothelial Growth Factors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0M1OwzAMAOAKgdgYvALKAcGpUn6WtD2iaTCkCXaAc-Qm7hpo05F0Gnt7yhjiZMv6bNk-ScZMyiwVXMnTIadZntKp4KPkIsZ3StmU0el5MmJU5EXB2TjR869NwBhd50lXkVXonK8aaFvou7An4O1PDfzadWv0zpDZvu8-nMdInCcr6B36PpKd62uyQLCHjmc0H2QG3mC4TM4qaCJeHeMkeXuYv84W6fLl8Wl2v0xrrvI-tYWlWZZBWRjOBaDNFEgrCqxKUVYWbS4EK8uKqakyEk3OaVFyCSI30oChYpLc_s7dhO5zi7HXrYsGmwY8dtuoVZHLXCg-wOsj3JYtWr0JroWw138vGcDNEUA00FRhuMPFfzdswlk2sLtfVrt1vXMBtTkcPDwTIZhaS600E6oQ3zJ2ehI</recordid><startdate>19990601</startdate><enddate>19990601</enddate><creator>ZHONG CHEN</creator><creator>MALHOTRA, P. S</creator><creator>MCCULLAGH, L</creator><creator>MOUSA, S</creator><creator>QUEZADO, M</creator><creator>HERSCHER, L. L</creator><creator>VAN WAES, C</creator><creator>THOMAS, G. R</creator><creator>ONDREY, F. G</creator><creator>DUFFEY, D. C</creator><creator>SMITH, C. W</creator><creator>ENAMORADO, I</creator><creator>YEH, N. T</creator><creator>KROOG, G. S</creator><creator>RUDY, S</creator><general>American Association for Cancer Research</general><scope>IQODW</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>19990601</creationdate><title>Expression of Proinflammatory and Proangiogenic Cytokines in Patients with Head and Neck Cancer</title><author>ZHONG CHEN ; MALHOTRA, P. S ; MCCULLAGH, L ; MOUSA, S ; QUEZADO, M ; HERSCHER, L. L ; VAN WAES, C ; THOMAS, G. R ; ONDREY, F. G ; DUFFEY, D. C ; SMITH, C. W ; ENAMORADO, I ; YEH, N. T ; KROOG, G. S ; RUDY, S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h268t-d9d0777ab9c223aed76a5d39efb3bfded8331bbf1646c5ec8209b25a38c5cac03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Acute-Phase Reaction - immunology</topic><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - secretion</topic><topic>Cytokines - metabolism</topic><topic>Cytokines - secretion</topic><topic>Endothelial Growth Factors - metabolism</topic><topic>Endothelial Growth Factors - secretion</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Fibroblast Growth Factor 2 - metabolism</topic><topic>Fibroblast Growth Factor 2 - secretion</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor - metabolism</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor - secretion</topic><topic>Head and Neck Neoplasms - metabolism</topic><topic>Head and Neck Neoplasms - secretion</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Inflammation - metabolism</topic><topic>Interleukin-1 - metabolism</topic><topic>Interleukin-1 - secretion</topic><topic>Interleukin-6 - metabolism</topic><topic>Interleukin-6 - secretion</topic><topic>Interleukin-8 - metabolism</topic><topic>Interleukin-8 - secretion</topic><topic>Lymphokines - metabolism</topic><topic>Lymphokines - secretion</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Otorhinolaryngology (head neck, general aspects and miscellaneous)</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Prospective Studies</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><topic>Vascular Endothelial Growth Factor A</topic><topic>Vascular Endothelial Growth Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ZHONG CHEN</creatorcontrib><creatorcontrib>MALHOTRA, P. S</creatorcontrib><creatorcontrib>MCCULLAGH, L</creatorcontrib><creatorcontrib>MOUSA, S</creatorcontrib><creatorcontrib>QUEZADO, M</creatorcontrib><creatorcontrib>HERSCHER, L. L</creatorcontrib><creatorcontrib>VAN WAES, C</creatorcontrib><creatorcontrib>THOMAS, G. R</creatorcontrib><creatorcontrib>ONDREY, F. G</creatorcontrib><creatorcontrib>DUFFEY, D. C</creatorcontrib><creatorcontrib>SMITH, C. W</creatorcontrib><creatorcontrib>ENAMORADO, I</creatorcontrib><creatorcontrib>YEH, N. T</creatorcontrib><creatorcontrib>KROOG, G. S</creatorcontrib><creatorcontrib>RUDY, S</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>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ZHONG CHEN</au><au>MALHOTRA, P. S</au><au>MCCULLAGH, L</au><au>MOUSA, S</au><au>QUEZADO, M</au><au>HERSCHER, L. L</au><au>VAN WAES, C</au><au>THOMAS, G. R</au><au>ONDREY, F. G</au><au>DUFFEY, D. C</au><au>SMITH, C. W</au><au>ENAMORADO, I</au><au>YEH, N. T</au><au>KROOG, G. S</au><au>RUDY, S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of Proinflammatory and Proangiogenic Cytokines in Patients with Head and Neck Cancer</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>1999-06-01</date><risdate>1999</risdate><volume>5</volume><issue>6</issue><spage>1369</spage><epage>1379</epage><pages>1369-1379</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Altered immune, inflammatory, and angiogenesis responses are observed in patients with head and neck squamous cell carcinoma
(HNSCC), and many of these responses have been linked with aggressive malignant behavior and a decrease in prognosis. In this
study, we examined the hypothesis that HNSCC cells produce cytokines that regulate immune, inflammatory, and angiogenesis
responses. We identified important regulatory cytokines in supernatants of well-defined and freshly cultured HNSCC cell lines
by ELISA and determined whether these cytokines are detected in tumor cell lines and tissue specimens by immunohistochemistry.
The serum concentration of the cytokines and cytokine-dependent acute phase inflammatory responses ( i.e. , fibrinogen, C-reactive protein, and erythrocyte sedimentation rate) from patients with HNSCC was determined, and the potential
relationship of serum cytokine levels to tumor volume was analyzed. Cytokines interleukin (IL)-1α, IL-6, IL-8, granulocyte-macrophage
colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor were detected
in similar concentration ranges in the supernatants of a panel of established University of Michigan squamous cell carcinoma
(UM-SCC) cell lines and supernatants of freshly isolated primary HNSCC cultures. Evidence for the expression of IL-1α, IL-6,
IL-8, granulocyte-macrophage colony-stimulating factor, and VEGF in HNSCC cells within tumor specimens in situ was obtained by immunohistochemistry. In a prospective comparison of the cytokine level and cytokine-inducible acute-phase
proteins in serum, we report that cytokines IL-6, IL-8, and VEGF were detected at higher concentrations in the serum of patients
with HNSCC compared with patients with laryngeal papilloma or age-matched control subjects (at P < 0.05). The serum concentrations of IL-8 and VEGF were found to be weakly correlated with large primary tumor volume (R 2 = 0.2 and 0.4, respectively). Elevated IL-1- and IL-6-inducible acute-phase responses were also detected in cancer patients
but not in patients with papilloma or control subjects (at P < 0.05). We therefore conclude that cytokines important in proinflammatory and proangiogenic responses are detectable in
cell lines, tissue specimens, and serum from patients with HNSCC. These cytokines may increase the pathogenicity of HNSCC
and prove useful as biomarkers or targets for therapy.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>10389921</pmid><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Clinical cancer research, 1999-06, Vol.5 (6), p.1369-1379 |
| issn | 1078-0432 1557-3265 |
| language | eng |
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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Acute-Phase Reaction - immunology Adult Aged Biological and medical sciences Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - secretion Cytokines - metabolism Cytokines - secretion Endothelial Growth Factors - metabolism Endothelial Growth Factors - secretion Enzyme-Linked Immunosorbent Assay Female Fibroblast Growth Factor 2 - metabolism Fibroblast Growth Factor 2 - secretion Granulocyte-Macrophage Colony-Stimulating Factor - metabolism Granulocyte-Macrophage Colony-Stimulating Factor - secretion Head and Neck Neoplasms - metabolism Head and Neck Neoplasms - secretion Humans Immunohistochemistry Inflammation - metabolism Interleukin-1 - metabolism Interleukin-1 - secretion Interleukin-6 - metabolism Interleukin-6 - secretion Interleukin-8 - metabolism Interleukin-8 - secretion Lymphokines - metabolism Lymphokines - secretion Male Medical sciences Middle Aged Otorhinolaryngology (head neck, general aspects and miscellaneous) Otorhinolaryngology. Stomatology Prospective Studies Tumor Cells, Cultured Tumors Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors |
| title | Expression of Proinflammatory and Proangiogenic Cytokines in Patients with Head and Neck Cancer |
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