Significance of interleukin-6 (IL-6) in breast cancer (review)

Abstract

Cytokines are factors that are known to have both tumor-promoting and inhibitory effects on breast cancer growth depending presumably on their relative concentrations and the presence of other modulating factors. Different cytokines play an important role in controlling the immune system. Interleukin-6 (IL-6) is a pleiotropic cytokine with obviously tumor-promoting and tumor-inhibitory effects. Here, we review the role of IL-6 in in vitro experiments of breast tumor cells, in breast tumor tissues (BTs) and assess its potential as a prognostic indicator in breast cancer patients. A literature search was conducted using PubMed, restricted to articles published in English language. In summary, results regarding the effect of IL-6 on breast tumor cells and on BTs are not unique indicating both tumor-promoting and inhibitory effects of IL-6. Concerning patients' serum IL-6 levels, data are surprisingly unique showing IL-6 to be a negative prognosticator in breast tumor patients.

Active and passive smoking, IL6, ESR1, and breast cancer risk

“…Smoking is associated with increased serum levels of the cytokine IL-6 and C-reactive protein (CRP) [13]. Several small case-control studies have suggested serum IL-6 is increased in women with breast cancer [14]. Recently, Il'yasova et al [15] reported increased serum CRP was associated with incident breast cancer in a cohort of post-menopausal women.…”

Loss of monocyte chemoattractant protein-1 expression delays mammary tumorigenesis and reduces localized inflammation in the C3(1)/SV40Tag triple negative breast cancer model

“…13 There are consistent data showing increased levels of IL-6 in breast cancer patients when compared with healthy controls and increased levels of IL-6 have also been correlated with clinical tumor stage, lymph node infiltration and recurrent disease. 46 IL-6 levels have also been associated with poor prognosis for time-to-progression and death in advanced stage patients. 47 In summary, we report for the first time that ablation of MCP-1 expression through genetic deletion delays mammary tumorigenesis and downregulates localized inflammation in the C3(1)/SV40Tag model of TNBC.…”

Correlation of Levels of IL-6 with Tumor Burden and Receptor Status in Patients of Locally Advanced Carcinoma Breast

“…Various studies have shown that the disease usually takes aggressive course where the IL-6 level is found to be elevated thereby indicating possibility of it being used as prognostic marker [9]. It is accepted that IL-6 promotes tumoral growth by upregulating antiapoptotic and angiogenic proteins in tumor cells [4][5][6]. Levels of IL-6 are reported to be considerably high in cancer patients compared to healthy control subjects [7,8].…”

“…According to a comprehensive review on the role of Il-6 in carcinogenesis, by Knüpfer and Preiss [6], serum IL-6 emerged as a negative prognosticator in breast cancer patients. Our data from Indian subset of patients also supports the same by virtue of increasing Il-6 titers with advanced stage, adipose tissue invasion, mitotic index and axillary lymph node involvement in breast cancer patients.…”

“…Interleukin-6 (IL-6) is mainly secreted by fibroblasts, macrophages and lymphocytes (mainly TH2 cells). It promotes tumor growth by up-regulating antiapoptotic and angiogenic proteins in tumor cells [4][5][6]. Serum interleukin-6 values have been shown to be significantly more in patients with breast cancer as compared to normal healthy women, which was correlated with clinical stage of disease and poor survival [7][8][9].…”