Significance of interleukin-33 and its related cytokines in patients with breast cancers.

Jia-Xin Shen,Jia-Lin Hu,Jing Liu,Wen-He Huang,Guo-Jun Zhang

doi:10.3389/fimmu.2014.00141

Abstract

Interleukin-33 (IL-33) is a recently identified cytokine, an important member of the interleukin-1 family. IL-33 binds to its receptor ST2 to induce type 2 cytokines and exert both pro-inflammatory and protective functions in host defense and disease. Murine breast carcinoma models suggest disruption of ST2 signaling may enhance the anti-tumor immune response, suggesting IL-33 impedes anti-tumor immunity. However, the role of IL-33 in patients with breast cancers (BC) is not elucidated. We detected the expression of IL-33 in tumor tissue, and IL-33 and its related cytokines in serum from BC patients. Using Luminex and immunohistochemistry methods, we found that serum levels of IL-33 were nearly twofold higher in patients with BC, compared to patients with benign breast diseases. In cancer tissues, expression of IL-33 was higher than matched normal breast tissues from the same patients, and was also associated with a well-differentiated phenotype, HER2 overexpression, more lymph nodes involvement, and a family history of malignant carcinoma. These results suggest that IL-33 may play an important role in the progress of BC and may be a useful biomarker for predicting the progress and metastasis of BC.

Highlights

Breast cancer (BC) is the second leading cause of cancer-related deaths amongst women in the United States, and morbidity and mortality of this disease increases each year [1]
In patients who showed lower Ki-67 expression, the serum levels of IL-33 were higher than the high Ki-67-expressing group (43.74 ± 19.40 pg/ml vs. 34.86 ± 9.86 pg/ml, p = 0.021)
IL-33 has been characterized as a potent inducer of T helper (Th) 2 immune responses, and is an important mediator for mucosal healing and epithelial

Summary

Introduction

Breast cancer (BC) is the second leading cause of cancer-related deaths amongst women in the United States, and morbidity and mortality of this disease increases each year [1]. The interleukin-1 (IL-1) family is a growing group of cytokines, consisting of at least 11 members, and the balance between proand anti-inflammatory cytokines is crucial in the pathogenesis of many human diseases [3]. IL-33 is an endogenous ligand for the ST2/T1 receptor, and depending on the cellular and cytokine context, participates in many immune diseases with dual, pro-inflammatory, or protective roles. IL-33 induces T cells to produce IL-4, IL-5, and IL-13, and potently induces pro-inflammatory cytokines and chemokines through a Th2-dependent pathway, and promotes Th1-type responses [5]. Deletion of IL-33/ST2 function enhances cytotoxicity of NK cells and increases levels of TNF-α, IFN-γ, and IL-17, and systemic pro-inflammatory cytokines, leading to attenuated tumor growth [8]

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