Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
Cancer Cell. 2011 Sep 13;20(3):300-14. doi: 10.1016/j.ccr.2011.08.012.
Primary tumors have been shown to prepare distal organs for later colonization of metastatic cells by stimulating organ-specific infiltration of bone marrow derived cells. Here we demonstrate that neutrophils accumulate in the lung prior to the arrival of metastatic cells in mouse models of breast cancer. Tumor-entrained neutrophils (TENs) inhibit metastatic seeding in the lungs by generating H(2)O(2) and tumor secreted CCL2 is a critical mediator of optimal antimetastatic entrainment of G-CSF-stimulated neutrophils. TENs are present in the peripheral blood of breast cancer patients prior to surgical resection but not in healthy individuals. Thus, whereas tumor-secreted factors contribute to tumor progression at the primary site, they concomitantly induce a neutrophil-mediated inhibitory process at the metastatic site.
原发肿瘤通过刺激骨髓来源细胞向特定器官浸润，为转移性细胞的后续定植做准备。在这里，我们证明了在乳腺癌小鼠模型中，转移性细胞到达之前，中性粒细胞会在肺部聚集。肿瘤诱导的中性粒细胞（TEN）通过产生 H2O2 来抑制肺部的转移定植，肿瘤分泌的 CCL2 是 G-CSF 刺激的中性粒细胞最佳转移诱导的关键介质。TEN 存在于乳腺癌患者手术切除前的外周血中，但不存在于健康个体中。因此，尽管肿瘤分泌的因子有助于原发性肿瘤的进展，但它们同时在转移部位诱导了中性粒细胞介导的抑制过程。
