Breast cancer subtypes express distinct receptor repertoires for tumor-associated macrophage derived cytokines

Abstract

Infiltration of the tumor microenvironment by macrophages is associated with poor outcomes in breast cancer and other solid tumors, however the identity and roles of many of the soluble factors these macrophages produce remains to be elucidated in detail. In addition to producing angiogenic factors (e.g. VEGF), proteases (e.g. MMP9) and immunomodulatory factors (e.g. IL10) which, by modifying the local microenvironment, likely contribute to progression in the majority of solid tumors, we have evaluated the extent to which macrophage cytokines may differentially affect distinct breast cancer subtypes. We identified 23 cytokines produced in a culture model of human tumor-associated macrophages and report that basal and luminal breast cancer cell lines express different repertoires of receptors for these cytokines. These data suggest that tumor-associated macrophages make specific contributions to different breast cancer subtypes and that understanding the importance of these interactions will be crucial to developing subtype-specific therapies targeting the macrophage component of the breast tumor microenvironment.