Expression of proinflammatory and proangiogenic cytokines in patients withhead and neck cancer

Altered immune, inflammatory, and angiogenesis responses are observed in pa tients with head and neck squamous cell carcinoma (HNSCC), and many of thes e responses have been linked with aggressive malignant behavior and a decre ase in prognosis. in this study, we examined the hypothesis that HNSCC cell s produce cytokines that regulate immune, inflammatory, and angiogenesis re sponses. We identified important regulatory cytokines in supernatants of we ll-defined and freshly cultured HNSCC cell lines by ELISA and determined wh ether these cytokines are detected in tumor cell lines and tissue specimens by immunohistochemistry. The serum concentration of the cytokines and cyto kine-dependent acute phase inflammatory responses (i.e., fibrinogen, C-reac tive 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 OL)-1 alpha, IL-6, IL-8, g ranulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothel ial growth factor (VEGF), and basic fibroblast growth factor were detected in similar concentration ranges in the supernatants of a panel of establish ed University of Michigan squamous cell carcinoma (UM-SCC) cell lines and s upernatants of freshly isolated primary HNSCC cultures. Evidence for the ex pression of IL-1 alpha, IL-6, IL-8, granulocyte-macrophage colony-stimulati ng factor, and VEGF in HNSCC cells within tumor specimens in situ was obtai ned by immunohistochemistry. In a prospective comparison of the cytokine le vel and cytokine-inducible acute-phase proteins in serum, we report that cy tokines IL-6, IL-8, and VEGF were detected at higher concentrations in the serum of patients with HNSCC compared with patients with laryngeal papillom a or age-matched control subjects (at P < 0,05), The serum concentrations o f 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-inducibl e acute-phase responses were also detected in cancer patients but not in pa tients with papilloma or control subjects (at P < 0,05), We therefore concl ude that cytokines important in proinflammatory and proangiogenic responses are detectable in cell lines, tissue specimens, and serum from patients wi th HNSCC. These cytokines may increase the pathogenicity of HNSCC and prove useful as biomarkers or targets for therapy.