Breast Cancer Progression: A “Vicious Cycle” of Pro-Malignancy Activities is Mediated by Inflammatory Cells, Chemokines and Cytokines

Abstract

Breast cancer progression is a multi-step process, affected by intrinsic, as well as by microenvironmental factors. The inflammatory milieu of breast tumors, comprising of cells, chemokines and cytokines, was recently suggested to have a major role in this process. The current chapter addresses the presence of these elements in breast tumors, and their roles in the malignancy and metastatic fate of breast cancer. First, the presence of Tumor-Associated Macrophages (TAM), and the array of tumor-promoting activities that they exert in breast tumors, is described. Thereafter, the inflammatory chemokines CCL2 (MCP-1), CCL5 (RANTES) and CXCL8 (Interleukin 8) are addressed, followed by description of the expression and roles of inflammatory cytokines, which are monocyte/macrophage-derived, namely Interleukin 1 (IL-1), Tumor Necrosis Factor α (TNFα) and Interleukin 6 (IL-6). Throughout the chapter, major emphasis is put on the manner by which the different inflammatory mediators cross-interact with each other, as well as with the tumor cells, together establishing an inflammatory microenvironment that consists of an extensive network of pro-malignancy activities.