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 neck squamous cell carcinoma (HNSCC) tumor specimens and normal control specimens.


METHODS
HNSCC and control tissue specimens were analyzed qualitatively using immunohistochemistry and quantitatively using immunoassays.


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 and receptors in tissue homogenates (mean levels +/- standard error of the mean, in pg/mg of total protein) indicated that: (1) TNF-alpha levels 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 elevated two- to four-fold 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, respectively).


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 microenvironment; targeting these receptors in cancer cells may provide a new approach to controlling tumor growth and metastasis.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D016022:Case-Control Studies; D002455:Cell Division; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D008233:Lymphotoxin-alpha / Q000032:analysis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology; D010610:Pharyngeal Neoplasms / Q000235:genetics / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism; D015854:Up-Regulation
D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha