Breast cancer is one of the leading causes of cancer related deaths in Australia. Tumour growth depends upon the recruitment and differentiation of cells that provide tumour vasculature-the “angiogenic switch.” Anti-angiogenic therapies can prolong patient survival; however, possess a range of serious side effects, including death. There is, therefore, an urgent need for the development of new anti-angiogenic therapies. The recruitment of cells that form tumour vasculature relies on a range of signaling molecules, including chemo-attractant cytokines, known as chemokines. As high levels of the C-C chemokine ligand-5 (CCL5, aka RANTES) occur in the tumors, and plasma, of advanced breast cancer patients, and because we know that endothelial cells express receptors for CCL5, such and CCR5; we hypothesized that pre-tumour vasculature cells are responding to a CCL5 gradient. Indeed we were able to show that breast cancer cells syngeneic for C57BL/6 (EO771) grown in CCR5 knockout mice showed reduced tumour growth, as well as, vascular defects, compared with WT and CCR1 knockout animals. As bone marrow (BM) derived inflammatory cells also express receptors for CCL5, CCR1 and CCR5, we then wanted to determine the contribution of these BM-derived cells in CCL/CCR mediated tumour growth. Surprisingly, BM transplantation (BMT) with CCR1 and CCR5 knockout BM, resulted in no difference in breast tumor growth. To then determine the contribution to tumour produced CCL5 to tumour growth in a breast cancer model, we carried out stable short hairpin (sh) RNA inhibition knockdown of CCL5 expression in the highly CCL5-expressing 4T1 breast cancer cell line. Notably, 4T1 cells which had low CCL5 had markedly reduced tumour growth. This strongly supports a role for CCL5/CCL5 signaling in breast tumour growth and angiogenesis. We are currently studying the role of this pathway in tumour endothelial cells in the hope that this may provide a new avenue for the development of future anti-angiogenic therapies.