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Interleukin-1 receptor antagonist in head and neck squamous cell carcinoma
S E von Biberstein1, J D Spiro, R Lindquist
1Department 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.
Insights
Head and neck squamous cell carcinoma shows increased interleukin-1 (IL-1) activity due to lower IL-1 receptor antagonist levels. This imbalance promotes tumor growth and metastasis.
Area of Science:
- Oncology
- Immunology
Background:
- Head and neck squamous cell carcinoma (HNSCC) is associated with overexpression of protumorigenic interleukin-1 (IL-1).
- This overexpression is hypothesized to result from decreased expression of IL-1 receptor antagonist by tumor cells.
Purpose of the Study:
- To investigate the expression of IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist in HNSCC.
- To determine the relationship between IL-1 activity and IL-1 receptor antagonist in HNSCC.
Main Methods:
- Immunohistochemical analysis of IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist in HNSCC tissues and normal specimens.
- Quantitative analysis of protein levels using Western blotting.
Main Results:
- IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist were detected in all 19 HNSCC specimens.
- Tumor tissues exhibited significantly higher levels of IL-1 alpha and IL-1 beta compared to normal tissues.
- The ratio of IL-1 to IL-1 receptor antagonist was markedly increased in HNSCC patients.
Conclusions:
- An elevated IL-1 index in HNSCC indicates an imbalance between IL-1 and its antagonist.
- This imbalance may drive the unrestricted growth and metastasis characteristic of HNSCC.