大网膜巨噬细胞分泌趋化因子配体，通过 CCR1 促进卵巢癌细胞在大网膜的定植。
Omental macrophages secrete chemokine ligands that promote ovarian cancer colonization of the omentum via CCR1.
机构信息
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Stanford School of Medicine, Stanford Cancer Institute, Stanford, CA, USA.
Genome Technology Center, Stanford, CA, USA.
出版信息
Commun Biol. 2020 Sep 22;3(1):524. doi: 10.1038/s42003-020-01246-z.
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.
大网膜是卵巢癌转移最常见的部位。在整个大网膜中发现了称为乳白色斑点的免疫细胞簇。然而，目前尚不清楚这些免疫细胞是否有助于卵巢癌转移。在这里，我们报告大网膜巨噬细胞通过分泌与趋化因子受体 1（CCR1）相互作用的趋化因子配体，促进卵巢癌细胞向大网膜的迁移和定植。我们发现巨噬细胞的耗竭减少了卵巢癌细胞在大网膜上的定植。从小鼠大网膜和肠系膜脂肪组织中分离出的巨噬细胞的 RNA 测序显示趋化因子配体 CCL6 在大网膜巨噬细胞中特异性富集。CCL6 和人同源物 CCL23 都是通过激活 ERK1/2 和 PI3K 途径促进卵巢癌细胞迁移所必需且充分的。重要的是，CCR1 抑制减少了卵巢癌的定植。这些发现表明了通过 CCR1 信号转导，大网膜巨噬细胞诱导卵巢癌细胞定植的关键机制。
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