Despite major advances in the treatment of breast cancer, metastatic disease still accounts for the majority of the mortality associated with this illness. The mechanisms behind tumour cell escape to distant organs such as lung, bone, liver and brain are poorly understood, and a role for inflammatory cells in the promotion of metastasis is even less clear. The literature remains contradictory regarding the effectiveness of targeting Tumour Associated Macrophages (TAMs), a predominant cell type in the tumour inflammatory infiltrate. We have demonstrated that targeting TAMs via their receptor for the growth factor CSF-1 unexpectedly increased metastasis to lung and bone in the 4T1.2 and EMT6.5 syngeneic mouse models of breast cancer. This was accompanied by an increase in circulating and Tumour Associated Neutrophils (TANs) and an increase in plasma levels of G-CSF. Targeting the receptor for G-CSF via treatment with an anti-G-CSFR antibody overcame this increase in metastasis and neutrophil accumulation. This project now aims to characterize the role of G-CSF in enhancing metastasis. We aim to identify the source of G-CSF in this model via shRNA knock-down in 4T1.2 tumour cells, and to characterize the in vivo immune response in the absence of tumour-derived G-CSF. Secondary to G-CSF, the contribution of stromal MMP-9 to the mobilization of immune cells to sites of metastatic spread is being characterized in MMP-9 deficient mice, as this protease has been demonstrated to be required for metastasis in our syngeneic tumour models. Ultimately, we aim to identify appropriate chemotherapy regimes that will be suitable for combination with anti-GCSFR therapy to improve the treatment of metastatic breast cancer.