Bulk RNA-Sequencing of Murine Normal and Tumor-Associated Omental and Mesenteric Macrophages
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 CCL6 chemokine ligand 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. Overall design: Omenta and Mesentery were excised from C57BL/6 mice (n=9) and processed as three separate groups (n=3 per group). Macrophages (CD45+CD11b+F4/80+) cells from dissociated tissues were flow cytometry sorted and the RNA was sequenced