Metastasis-associated macrophages (MAM) promote persistent growth of breast cancer cells at the metastatic site and are, thus, an attractive therapeutic target to treat breast cancer metastasis, a leading cause of cancer-related death in women. However, the precise mechanisms behind MAM-mediated metastatic tumor outgrowth have not been fully elucidated. Using mouse models of metastatic breast cancer, we showed that MAMs uniquely expressed hepatocyte growth factor (HGF) in metastatic tumors. We also demonstrated that a selected population of cancer cells with high metastatic potential (cancer cells that can establish metastatic tumors in mice with higher number and incidence than parental cells) had higher expression of HGF receptor, MNNG HOS transforming gene (MET), and were more responsive to HGF released from macrophages compared with the parental cells. Blockade of MET signaling in cancer cells suppressed metastatic tumor expansion, in part, through activation of natural killer cells. Results from this study suggest an approach to prevent life-threatening metastatic tumor formation using blockade of MAM-induced MET signal activation in metastatic cancer cells.

中文翻译：

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具有高转移潜能的乳腺肿瘤细胞对巨噬细胞衍生的 HGF 过敏。

转移相关巨噬细胞 (MAM) 促进转移部位乳腺癌细胞的持续生长，因此是治疗乳腺癌转移的有吸引力的治疗靶点，这是女性癌症相关死亡的主要原因。然而，MAM 介导的转移性肿瘤生长背后的确切机制尚未完全阐明。使用转移性乳腺癌的小鼠模型，我们发现 MAM 在转移性肿瘤中独特地表达肝细胞生长因子 (HGF)。我们还证明了具有高转移潜能的选定癌细胞群（可以在小鼠中建立转移性肿瘤的癌细胞，其数量和发病率高于亲本细胞）具有更高的 HGF 受体表达，MNNG HOS 转化基因（MET），并且与亲代细胞相比，对巨噬细胞释放的 HGF 更敏感。阻断癌细胞中的 MET 信号通路部分地通过激活自然杀伤细胞来抑制转移性肿瘤的扩张。这项研究的结果表明了一种通过阻断 MAM 诱导的转移性癌细胞中的 MET 信号激活来预防危及生命的转移性肿瘤形成的方法。