Oncogene：肿瘤细胞招募中性粒细胞驱动肺转移

肾细胞癌(renal cell carcinoma)是成年人原发性肾肿瘤中最常见的类型，占肾肿瘤的70～80%，占肾恶性肿瘤的90%。多见于60岁左右的人群，男性多于女性。初诊时肿瘤限于肾内的患者，术后五年生存率可达70%以上，但侵及肾静脉或扩散至肾周围脂肪组织的患者，五年生存率仅5～20%。

肾细胞癌（RCC）定向转移至肺组织的具体机制至今仍然知之甚少。为了研究分析转移过程中的具体分子机制，López-Lago MA等研究人员将不同肺转移潜能的人源肾细胞种植到小鼠体内。基因表达分析显示不同转移性细胞转移至小鼠肺间质与中性粒细胞特异性侵润有关。相关研究论文发表在Oncogene杂志上。

分析表明，肿瘤细胞株转移活性与趋化因子的数量包括CXCL5和IL - 8水平呈负相关。去除这些细胞株中的CXCL5和IL - 8，使我们能够将肺组织中中性粒细胞的浸润与癌细胞转移活性的趋化因子的分泌联系起来。

进一步研究表明，与高转移细胞相比，人类嗜中性粒细胞对转移性能较低的肿瘤细胞有较高的细胞毒活性。总之，这些结果证实肿瘤分泌趋化因子招募中性粒细胞至肺组织，抑制趋化因子对中性粒细胞的招募作用能有效抑制肺转移，发挥抗肿瘤作用。

doi:10.1038/onc.2012.201
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Neutrophil chemokines secreted by tumor cells mount a lung antimetastatic response during renal cell carcinoma progression.

López-Lago MA, Posner S, Thodima VJ, Molina AM, Motzer RJ, Chaganti RS.

The mechanism by which renal cell carcinoma (RCC) colonizes the lung microenvironment during metastasis remains largely unknown. To investigate this process, we grafted human RCC cells with varying lung metastatic potential in mice. Gene expression profiling of the mouse lung stromal compartment revealed a signature enriched for neutrophil-specific functions that was induced preferentially by poorly metastatic cells. Analysis of the gene expression signatures of tumor cell lines showed an inverse correlation between metastatic activity and the levels of a number of chemokines, including CXCL5 and IL8. Enforced depletion of CXCL5 and IL8 in these cell lines enabled us to establish a functional link between lung neutrophil infiltration, secretion of chemokines by cancer cells and metastatic activity. We further show that human neutrophils display a higher cytotoxic activity against poorly metastatic cells compared with highly metastatic cells. Together, these results support a model in which neutrophils recruited to the lung by tumor-secreted chemokines build an antimetastatic barrier with loss of neutrophil chemokines in tumor cells acting as a critical rate-limiting step during lung metastatic seeding.