The interleukin-1 family of cytokines and receptors in human breast cancer: implications for tumor progression.

We have previously described the expression of interleukin cytokines (IL)-1alpha, IL-1beta, and IL-1 receptor antagonist (IL-1ra) in human breast cancer (HBC) tissue. Based on our previous studies, we hypothesize that the IL-1 family of cytokines, antagonists (IL-1ra) and receptors (IL-1RI and IL-1RII) are present within the human breast cancer (HBC) tumor microenvironment and that the IL-1 network of cytokines and receptors within the tumor microenvironment can control tumor cell subpopulation expression of other protumorigenic cytokines such as the angiogenic/growth factor, interleukin-8 (IL-8). To test this hypothesis we characterized the in vivo expression of the IL-1 network in HBC tissues and homogenates by immunohistochemistry (IHC) and ELISA.

In vitro demonstration of breast cancer tumor cell sub-populations based on interleukin-1/tumor necrosis factor induction of interleukin-8 expression.

Interleukin-8 (IL-8) has been identified as an angiogenesis factor (AF) as well as a tumor cell chemotactic factor and mitogen. Recent in vivo studies have demonstrated the expression of IL-8, IL-1 and TNF, as well their receptors, on various sub-populations of tumor cells in human breast cancer (HBC). Since pro-inflammatory cytokines such as IL-1 and TNF are known inducers of IL-8 in non-tumor cells, we hypothesize that IL-1/TNF may act as an IL-8 inducer in HBC, and thus enhance HBC tumor progression.