腎細(xì)胞癌(renal cell carcinoma)是成年人原發(fā)性腎腫瘤中最常見(jiàn)的類型,，占腎腫瘤的70～80%,，占腎惡性腫瘤的90%,。多見(jiàn)于60歲左右的人群,，男性多于女性。初診時(shí)腫瘤限于腎內(nèi)的患者,，術(shù)后五年生存率可達(dá)70%以上，但侵及腎靜脈或擴(kuò)散至腎周圍脂肪組織的患者,，五年生存率僅5～20%,。
腎細(xì)胞癌（RCC）定向轉(zhuǎn)移至肺組織的具體機(jī)制至今仍然知之甚少。為了研究分析轉(zhuǎn)移過(guò)程中的具體分子機(jī)制,，López-Lago MA等研究人員將不同肺轉(zhuǎn)移潛能的人源腎細(xì)胞種植到小鼠體內(nèi),。基因表達(dá)分析顯示不同轉(zhuǎn)移性細(xì)胞轉(zhuǎn)移至小鼠肺間質(zhì)與中性粒細(xì)胞特異性侵潤(rùn)有關(guān),。相關(guān)研究論文發(fā)表在Oncogene雜志上,。
分析表明，腫瘤細(xì)胞株轉(zhuǎn)移活性與趨化因子的數(shù)量包括CXCL5和IL - 8水平呈負(fù)相關(guān),。去除這些細(xì)胞株中的CXCL5和IL - 8,，使我們能夠?qū)⒎谓M織中中性粒細(xì)胞的浸潤(rùn)與癌細(xì)胞轉(zhuǎn)移活性的趨化因子的分泌聯(lián)系起來(lái)。
進(jìn)一步研究表明,，與高轉(zhuǎn)移細(xì)胞相比,，人類嗜中性粒細(xì)胞對(duì)轉(zhuǎn)移性能較低的腫瘤細(xì)胞有較高的細(xì)胞毒活性?？傊?，這些結(jié)果證實(shí)腫瘤分泌趨化因子招募中性粒細(xì)胞至肺組織,，抑制趨化因子對(duì)中性粒細(xì)胞的招募作用能有效抑制肺轉(zhuǎn)移,，發(fā)揮抗腫瘤作用。（生物谷：Bioon.com）
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.
