The study investigates the role of CCL2 in recruiting inflammatory monocytes (IMs) to facilitate breast tumor metastasis. The authors found that Gr1+ IMs are preferentially recruited to pulmonary metastases but not primary mammary tumors, a process also observed in human breast cancer. The recruitment of these CCR2-expressing IMs and subsequent differentiation into metastasis-associated macrophages (MAMs) is dependent on CCL2 synthesized by both tumor and stromal cells. Inhibition of CCL2/CCR2 signaling using anti-CCL2 antibodies blocks IM recruitment and inhibits metastasis in vivo, prolonging the survival of tumor-bearing mice. Depletion of tumor cell-derived CCL2 also inhibits metastatic seeding. IMs promote tumor cell extravasation through the production of VEGF. CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer. The study provides a mechanistic link between these clinical associations and suggests new therapeutic targets for treating metastatic breast disease.The study investigates the role of CCL2 in recruiting inflammatory monocytes (IMs) to facilitate breast tumor metastasis. The authors found that Gr1+ IMs are preferentially recruited to pulmonary metastases but not primary mammary tumors, a process also observed in human breast cancer. The recruitment of these CCR2-expressing IMs and subsequent differentiation into metastasis-associated macrophages (MAMs) is dependent on CCL2 synthesized by both tumor and stromal cells. Inhibition of CCL2/CCR2 signaling using anti-CCL2 antibodies blocks IM recruitment and inhibits metastasis in vivo, prolonging the survival of tumor-bearing mice. Depletion of tumor cell-derived CCL2 also inhibits metastatic seeding. IMs promote tumor cell extravasation through the production of VEGF. CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer. The study provides a mechanistic link between these clinical associations and suggests new therapeutic targets for treating metastatic breast disease.