Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer

Zhong Chen, Pramit S. Malhotra, Giovana Thomas, Frank G. Ondrey, Dianne C. Duffey, Conrad W. Smith, Ileana Enamorado, Ning T. Yeh, Glenn S. Kroog, Susan Rudy, Linda McCullagh, Shaker Mousa, Matha Quezado, Laurie L. Herscher, Carter Van Waes

Research output: Contribution to journalArticle

383 Citations (Scopus)

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 (R2 = 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.

Original languageEnglish
Pages (from-to)1369-1379
Number of pages11
JournalClinical Cancer Research
Volume5
Issue number6
StatePublished - Jun 1 1999
Externally publishedYes

Fingerprint

Head and Neck Neoplasms
Cytokines
Interleukin-8
Vascular Endothelial Growth Factor A
Interleukin-6
Serum
Interleukin-1
Acute-Phase Reaction
Papilloma
Granulocyte-Macrophage Colony-Stimulating Factor
Tumor Burden
Cell Line
Immunohistochemistry
Carcinoma, squamous cell of head and neck
Acute-Phase Proteins
Blood Sedimentation
Fibroblast Growth Factor 2
Tumor Cell Line
C-Reactive Protein
Fibrinogen

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Chen, Z., Malhotra, P. S., Thomas, G., Ondrey, F. G., Duffey, D. C., Smith, C. W., ... Van Waes, C. (1999). Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer. Clinical Cancer Research, 5(6), 1369-1379.

Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer. / Chen, Zhong; Malhotra, Pramit S.; Thomas, Giovana; Ondrey, Frank G.; Duffey, Dianne C.; Smith, Conrad W.; Enamorado, Ileana; Yeh, Ning T.; Kroog, Glenn S.; Rudy, Susan; McCullagh, Linda; Mousa, Shaker; Quezado, Matha; Herscher, Laurie L.; Van Waes, Carter.

In: Clinical Cancer Research, Vol. 5, No. 6, 01.06.1999, p. 1369-1379.

Research output: Contribution to journalArticle

Chen, Z, Malhotra, PS, Thomas, G, Ondrey, FG, Duffey, DC, Smith, CW, Enamorado, I, Yeh, NT, Kroog, GS, Rudy, S, McCullagh, L, Mousa, S, Quezado, M, Herscher, LL & Van Waes, C 1999, 'Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer', Clinical Cancer Research, vol. 5, no. 6, pp. 1369-1379.
Chen Z, Malhotra PS, Thomas G, Ondrey FG, Duffey DC, Smith CW et al. Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer. Clinical Cancer Research. 1999 Jun 1;5(6):1369-1379.
Chen, Zhong ; Malhotra, Pramit S. ; Thomas, Giovana ; Ondrey, Frank G. ; Duffey, Dianne C. ; Smith, Conrad W. ; Enamorado, Ileana ; Yeh, Ning T. ; Kroog, Glenn S. ; Rudy, Susan ; McCullagh, Linda ; Mousa, Shaker ; Quezado, Matha ; Herscher, Laurie L. ; Van Waes, Carter. / Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer. In: Clinical Cancer Research. 1999 ; Vol. 5, No. 6. pp. 1369-1379.
@article{6fa501f3a3b74be0b3c4b903e98eb176,
title = "Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer",
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 (R2 = 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.",
author = "Zhong Chen and Malhotra, {Pramit S.} and Giovana Thomas and Ondrey, {Frank G.} and Duffey, {Dianne C.} and Smith, {Conrad W.} and Ileana Enamorado and Yeh, {Ning T.} and Kroog, {Glenn S.} and Susan Rudy and Linda McCullagh and Shaker Mousa and Matha Quezado and Herscher, {Laurie L.} and {Van Waes}, Carter",
year = "1999",
month = "6",
day = "1",
language = "English",
volume = "5",
pages = "1369--1379",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "6",

}

TY - JOUR

T1 - Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer

AU - Chen, Zhong

AU - Malhotra, Pramit S.

AU - Thomas, Giovana

AU - Ondrey, Frank G.

AU - Duffey, Dianne C.

AU - Smith, Conrad W.

AU - Enamorado, Ileana

AU - Yeh, Ning T.

AU - Kroog, Glenn S.

AU - Rudy, Susan

AU - McCullagh, Linda

AU - Mousa, Shaker

AU - Quezado, Matha

AU - Herscher, Laurie L.

AU - Van Waes, Carter

PY - 1999/6/1

Y1 - 1999/6/1

N2 - 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 (R2 = 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.

AB - 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 (R2 = 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.

UR - http://www.scopus.com/inward/record.url?scp=0033017066&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033017066&partnerID=8YFLogxK

M3 - Article

C2 - 10389921

AN - SCOPUS:0033017066

VL - 5

SP - 1369

EP - 1379

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 6

ER -