Project description: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.
Project description:Single cell RNA sequencing of macrophages harvested from omentum of mice 10 weeks after intra peritoneal inoculation of epithelial ovarian cancer cells.
Project description:Interventions: ICG-labelled omental appendices
Primary outcome(s): Detection rate of indocyanine green-labelled omental appendices
Study Design: Single arm Non-randomized
Project description:Single-cell RNA sequencing of 697 YFP+ CD64+ lamina propria macrophages isolated from Cx3cr1CreERT2.Rosa26-LSL-YFP mice 35 weeks after tamoxifen administration
Project description:The omentum is a critical intraperitoneal organ essential for peritoneal homeostasis, yet detailed characterization of its cellular composition remains limited by the lack of validated markers. Here, we employed single-cell RNA sequencing to systematically define cellular heterogeneity in naive and activated mouse omentum from both sexes. Our analysis identified previously uncharacterized immune and stromal cell subsets, including three macrophage subtypes with activation-dependent gene expression patterns, implying specialized roles in inflammation and immune regulation. Comparative analysis revealed marked transcriptional differences between omental and peritoneal macrophages, underscoring tissue-specific microenvironments. Additionally, sexually dimorphic gene expression in omental stromal cells correlated with peritoneal macrophage polarization, indicating sex-specific regulatory mechanisms. Critically, macrophages from omentum of female mice with ovarian cancer metastases showed unique gene signatures associated with tumor migration and invasion. Collectively, we provide the first comprehensive atlas of omental cell populations stratified by sex and activation state, offering novel insights into peritoneal immunity and identifying potential therapeutic targets for inflammatory and metastatic diseases.