Systemic inflammation increases breast cancer risk, promotes breast cancer progression, and reduces survival. Inflammation is a persistent state that involves the chronic activation of the immune system. A new study has reported that suppression of the pro-inflammatory cytokines IL-6 and IL-8 reduces the growth and metastasis of triple negative (ER-/PR-/HER2-) breast cancer.
The study was designed to investigate how inflammation influences triple negative breast cancer growth and survival. Triple negative breast cancer is an aggressive subtype of breast cancer that is estrogen receptor negative (ER-), progesterone receptor negative (PR-), and human epidermal growth factor receptor 2 negative (HER2-). To conduct the study, the authors used a type of database analysis to identify 32 inflammation-related genes that are differentially expressed in triple negative breast cancer cells. Ten of these genes were shown to be critical for anchorage-independent growth. Anchorage-independent cells do not require a solid substratum (such as the solid surface of a culture dish) for growth, and can be grown in suspension or soft media in which they float freely. The presence of cells with anchorage-independent growth indicates that a tumor has metastatic potential.
The authors then demonstrated that a specific signaling pathway (the LPA-LPAR2-EZH2 NF-kappaB signaling cascade) is essential for the expression of IL-6 (interleukin 6), IL-8 (interleukin 8) and CXCL1 (chemokine (C-X-C motif) ligand 1) in triple negative cells. IL-6 and IL-8 are cytokines associated with inflammation. In a series of experiments, the authors showed that concurrent inhibition of IL-6 and IL-8 expression sharply reduced colony formation and survival of triple negative cells. IL-6 and IL-8 inhibition also interfered with the establishment of triple negative tumor grafts and reduced tumor growth in an animal model of breast cancer. In addition, analysis of breast cancer patient specimens showed that the degree of IL-6 and IL-8 expression predicted the survival times of the patients. The authors conclude that use of dual inhibition of IL-6/IL-8 signaling as a treatment could improve outcomes for triple negative breast cancer patients.
Please see our articles on inflammation and what triple negative patients and survivors should eat for more information.