Interleukin-1 receptor antagonist in head and neck squamous cell carcinoma
S. E. von Biberstein, J. D. Spiro, R. Lindquist and D. L. Kreutzer
Department of Surgery, University of Connecticut Health Center, Farmington, USA.
BACKGROUND: We hypothesized that in head and neck squamous cell carcinoma,
the overexpression of protumorigenic interleukin-1 (IL-1) activity within
the tumor tissue is a result of decreased expression of the specific
antagonist or inhibitor (ie, IL-1 receptor antagonist) by the tumor cells.
Ultimately, this local overexpression of IL-1 activity increases tumor
growth and metastasis. DESIGN: To test our hypotheses, immunologic analysis
for IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist was performed on
histologic sections and tumor homogenates of human head and neck squamous
cell carcinomas. SETTING: University teaching hospital. PATIENTS OR OTHER
PARTICIPANTS: Normal and tumor specimens were obtained from patients
undergoing surgical resections of the head and neck for benign and
malignant disease. RESULTS: Immunohistochemical analysis demonstrated the
presence of IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist within
tumor cells and inflammatory cells in the tumor stroma in 19 of 19 tumor
specimens. Quantitatively, IL-1 alpha was present in 19 of 19 tumor
specimens (1.97 +/- 0.46 ng/mg of total protein [mean +/- SD]) and 5 of 9
normal specimens (0.23 +/- 0.12 ng/mg of total protein). All specimens
contained IL-1 beta in detectable quantities (1.60 +/- 0.29 ng/mg of total
protein in tumor specimens and 0.189 +/- 0.04 ng/mg of total protein in
normal specimens). All specimens contained IL-1 receptor antagonist (368.87
+/- 57.63 ng/mg of total protein in tumor specimens and 585.10 +/- 166.03
ng/mg of total protein in normal specimens). The mean total IL-1/IL-1
receptor antagonist ratio was 13.26 +/- 2.31 in patients with cancer
compared with 0.997 +/- 0.26 in normal patients. CONCLUSIONS: The increased
IL-1 index in the cancer state compared with the normal state reflects an
imbalance of IL-1 and IL-1 receptor antagonist, which may contribute to
unrestricted growth and metastasis of head and neck squamous cell
carcinoma.