Omental macrophages secrete chemokine ligands that promote ovarian cancer colonization of the omentum via CCR1

The omentum is the most common site of ovarian cancer metastasis. Immune cell clusters called milky spots are found throughout the omentum. It is however unknown if these immune cells contribute to ovarian cancer metastasis. Here we report that omental macrophages promote the migration and colonization of ovarian cancer cells to the omentum through the secretion of chemokine ligands that interact with chemokine receptor 1 (CCR1). We found that depletion of macrophages reduces ovarian cancer colonization of the omentum. RNA-sequencing of macrophages isolated from mouse omentum and mesenteric adipose tissue revealed a specific enrichment of chemokine ligand CCL6 in omental macrophages. CCL6 and the human homolog CCL23 were both necessary and sufficient to promote ovarian cancer migration by activating ERK1/2 and PI3K pathways. Importantly, inhibition of CCR1 reduced ovarian cancer colonization. These findings demonstrate a critical mechanism of omental macrophage induced colonization by ovarian cancer cells via CCR1 signaling. Krishnan et al. find that CCR1 ligands CCL6 and CCL23 secreted by murine and human macrophages, respectively, enhance metastatic colonization of ovarian cancer cells to the omentum in manner dependent on chemokine receptor 1 (CCR1). This study suggests that targeting CCR1 or CCL23 in ovarian cancer may be a therapeutic strategy.