Experimental and clinical evidence suggests that tumor-associated macrophages (TAMs) play important roles in cancer progression. Here, we have characterized the ontogeny and function of TAM subsets in a mouse model of metastatic ovarian cancer that is representative for visceral peritoneal metastasis. We show that the omentum is a critical premetastatic niche for development of invasive disease in this model and define a unique subset of CD163+ Tim4+ resident omental macrophages responsible for metastatic spread of ovarian cancer cells. Transcriptomic analysis showed that resident CD163+ Tim4+ omental macrophages were phenotypically distinct and maintained their resident identity during tumor growth. Selective depletion of CD163+ Tim4+ macrophages in omentum using genetic and pharmacological tools prevented tumor progression and metastatic spread of disease. These studies describe a specific role for tissue-resident macrophages in the invasive progression of metastatic ovarian cancer. The molecular pathways of cross-talk between tissue-resident macrophages and disseminated cancer cells may represent new targets to prevent metastasis and disease recurrence.

中文翻译：

---

大网膜中的组织驻留巨噬细胞促进卵巢癌的转移扩散

实验和临床证据表明肿瘤相关巨噬细胞（TAM）在癌症进展中发挥重要作用。在这里，我们描述了代表内脏腹膜转移的转移性卵巢癌小鼠模型中 TAM 子集的个体发育和功能。我们表明，在该模型中，大网膜是侵袭性疾病发展的关键转移前生态位，并定义了负责卵巢癌细胞转移扩散的 CD163+ Tim4+ 常驻网膜巨噬细胞的独特子集。转录组分析表明，常驻 CD163+ Tim4+ 网膜巨噬细胞表型不同，并在肿瘤生长过程中保持其常驻身份。使用遗传和药理学工具选择性消耗网膜中的 CD163+ Tim4+ 巨噬细胞可防止肿瘤进展和疾病的转移性扩散。这些研究描述了组织驻留巨噬细胞在转移性卵巢癌侵袭性进展中的特定作用。组织驻留巨噬细胞和播散性癌细胞之间相互作用的分子途径可能代表预防转移和疾病复发的新靶点。