ENHANCED TUMOR-CELL EXPRESSION OF TUMOR-NECROSIS-FACTOR RECEPTORS IN HEAD AND NECK SQUAMOUS-CELL CARCINOMA

BACKGROUND: TO determine if tumor necrosis factor (TNF) receptors are upregulated in tumor cells, we measured the distribution and levels of TNF-alpha and TNF-beta, and TNF receptors RI and RII, in head and nec k squamous cell carcinoma (HNSCC) tumor specimens and normal control s pecimens. METHODS: HNSCC and control tissue specimens were analyzed qu alitatively using immunohistochemistry and quantitatively using immuno assays. RESULTS: Immunohistochemical analysis revealed that TNF-alpha, TNF-beta, TNF RI, and TNF RII antigens were associated predominately with tumor cells in the tissue. Quantitative analysis of TNF factors a nd receptors in tissue homogenates (mean levels +/- standard error of the mean, in pg/mg of total protein) indicated that: (1) TNF-alpha lev els in cancer patients were not statistically different from levels in normal tissues (7.27 +/- 0.91 versus 4.62 +/- 1.33, respectively, P < 0.11); (2) TNF-beta levels in cancer patients were one third of those in normal tissue (5.07 +/- 1.83 versus 16.06 +/- 3.26, respectively, P < 0.01); and (3) both TNF RI and TNF RII levels were consistently el evated two- to four-ford in the cancer tissue when compared to normal tissue levels (1,228.72 +/- 125.67 versus 650.33 +/- 187.70, P < 0.01; and 823.39 +/- 95.90 versus 230.03 +/- 153.01, P < 0.002, respectivel y). CONCLUSIONS: In HNSCC, enhanced expression of TNF receptors on the cancer cells occurs and is likely to contribute to the regulation of TNF and its activation of tumor cells within the tumor microenvironmen t; targeting these receptors in cancer cells may provide a new approac h to controlling tumor growth and metastasis.