Abstract 1160: Novel CSF-1 receptor ligand IL-34 modulates macrophage-breast cancer cell crosstalk

Abstract Crosstalk between stromal cells and malignant cells within the tumor microenvironment is important for tumorigenesis. According to current clinical and experimental evidence, tumor associated macrophages (TAMs) play a major role in tumor progression to metastasis in different cancers. In breast cancer, increased number of TAMs is associated with poor prognosis. Previous work in our laboratory has shown that depletion of TAMs by blocking colony-stimulating factor-1 (CSF-1) suppresses tumor growth, matrix metalloprotease production and further recruitment of macrophages in a MCF-7 breast cancer xenograft model. In this study, we aim to investigate Interleukin-34 (IL-34), a novel ligand for the colony stimulating factor-1 receptor (CSF-1R). IL-34 functions as a specific and independent ligand and as an agonist to the CSF-1R. Furthermore it is known to induce proliferation through mitogen activated protein kinase (MAPK) activation in macrophages and cancer cells. To date, nothing is known about the role of IL-34 in breast cancer and its effects on downstream signalling pathway modulation in cancer cell-macrophage crosstalk. Our real-time PCR data shows that in co-cultures with murine macrophages, human MCF-7 and MDA-MB-231 breast cancer cells express increased levels of IL-34. In addition, in vitro migration assays demonstrated that recombinant human and murine IL-34 significantly increases the migration of murine macrophages, MCF-7 and MDA-MB-231 breast cancer cells. IL-34 also increased the proliferation of murine macrophages and breast cancer cells. Experiments on the protein level demonstrated the activation of MAPK/ERK in murine macrophages and breast cancer cells by recombinant IL-34. These preliminary data indicate that TAM-breast cancer cell interactions induce IL-34 production associated with induction of proliferation and the migratory capacity of tumor and stromal cells, which together may influence the invasiveness of the developing tumor. Here we propose IL-34 as a target for the treatment of breast cancer which may affect the accumulation of TAMs and improve breast cancer prognosis. Citation Format: Sandun Gunawardhana, Karin Zins, Trevor Lucas, Dietmar Abraham. Novel CSF-1 receptor ligand IL-34 modulates macrophage-breast cancer cell crosstalk. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1160. doi:10.1158/1538-7445.AM2014-1160