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【Cancer research】短暂进入血循环的肿瘤细胞通过
It is unknown why only a minority of circulating tumor cells trapped in lung capillaries form metastases and involvement of immune cells remains uncertain. A novel model has been developed in this study showing that neutrophils regulate lung metastasis development through physical interaction and anchoring of circulating tumor cells to endothelium. Human melanoma cells were i.v. injected into nude mice leading to the entrapment of many cancer cells; however, 24 hours later, very few remained in the lungs. In contrast, injection of human neutrophils an hour after tumor cell injection increased cancer cell retention by ∼3-fold. Entrapped melanoma cells produced and secreted high levels of a cytokine called interleukin-8 (IL-8), attracting neutrophils and increasing tethering β2 integrin expression by 75% to 100%. Intercellular adhesion molecule-1 on melanoma cells and β2 integrin on neutrophils interacted, promoting anchoring to vascular endothelium. Decreasing IL-8 secretion from melanoma cells lowered extracellular levels by 20% to 50%, decreased β2 integrin on neutrophils by ∼50%, and reduced neutrophil-mediated extravasation by 25% to 60%, resulting in ∼50% fewer melanoma cells being tethered to endothelium and retained in lungs. Thus, transendothelial migration and lung metastasis development decreased by ∼50%, showing that targeting IL-8 in melanoma cells has the potential to decrease metastasis development by disrupting interaction with neutrophils. Cancer Res; 70(14); 6071–82. ©2010 AACR. 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 翻译
Transiently Entrapped Circulating Tumor Cells Interact with Neutrophils to Facilitate Lung Metastasis Development
短暂进入血循环的肿瘤细胞通过与中性粒细胞的相互作用促进肺癌的转移
It is unknown why only a minority of circulating tumor cells trapped in lung capillaries form metastases and involvement of immune cells remains uncertain.为什么只有少量循环肿瘤细胞进入肺毛细血管形成转移还不清楚，其中涉及的免疫细胞也不确定。
A novel model has been developed in this study showing that neutrophils regulate lung metastasis development through physical interaction and anchoring of circulating tumor cells to endothelium. 本研究研发了一个新模型显示，中性粒细胞通过物理作用和锚定循环肿瘤细胞到内皮细胞上来调节肺转移的进展。
Human melanoma cells were i.v. injected into nude mice leading to the entrapment of many cancer cells; however, 24 hours later, very few remained in the lungs. In contrast, injection of human neutrophils an hour after tumor cell injection increased cancer cell retention by ∼3-fold. 人黑色素瘤细胞被静注到裸鼠，导致许多癌细胞进入；然而24h后，很少保留在肺中。与之相比，肿瘤细胞注射后一小时后再注射人中性粒细胞，癌细胞滞留增加3倍。
Entrapped melanoma cells produced and secreted high levels of a cytokine called interleukin-8 (IL-8), attracting neutrophils and increasing tethering β2 integrin expression by 75% to 100%. Intercellular adhesion molecule-1 on melanoma cells and β2 integrin on neutrophils interacted, promoting anchoring to vascular endothelium. 进入的黑色素瘤细胞产生并分泌高水平的细胞因子IL-8；吸引中性粒细胞使系留的β2整合素表达增加75%-100%。在黑色素瘤细胞上的细胞间黏附分子-1和中性粒细胞上的β2整合素相互作用下，促进锚定到血管内皮上。
Decreasing IL-8 secretion from melanoma cells lowered extracellular levels by 20% to 50%, decreased β2 integrin on neutrophils by ∼50%, and reduced neutrophil-mediated extravasation by 25% to 60%, resulting in ∼50% fewer melanoma cells being tethered to endothelium and retained in lungs.黑色素瘤细胞分泌的IL-8减少，降低了细胞外水平20%-50%，中性粒细胞上的β2整合素降低到50%，使中性粒细胞介导的外渗减少至25%-60%，导致50%不到的黑色素瘤细胞被系留到内皮，留存在肺内。
Thus, transendothelial migration and lung metastasis development decreased by ∼50%, showing that targeting IL-8 in melanoma cells has the potential to decrease metastasis development by disrupting interaction with neutrophils. Cancer Res; 70(14); 6071–82. ©2010 AACR. 因此，跨内皮运动和肺转移进展减少至50%，显示了靶定黑色素瘤细胞的IL-8具有通过打破中性粒细胞相互作用，降低转移进展的潜能。Cancer Res; 70(14); 6071–82. ©2010 AACR.
编译
短暂进入血循环的肿瘤细胞通过与中性粒细胞的相互作用促进肺癌的转移
为什么只有少量循环肿瘤细胞进入肺毛细血管形成转移还不清楚，其中涉及的免疫细胞也不确定。本研究研发了一个新模型显示，中性粒细胞通过物理作用和锚定循环肿瘤细胞到内皮细胞上来调节肺转移的进展。人黑色素瘤细胞被静注到裸鼠，导致许多癌细胞进入；然而24h后，很少保留在肺中。与之相比，肿瘤细胞注射后一小时后再注射人中性粒细胞，癌细胞滞留增加3倍。进入的黑色素瘤细胞产生并分泌高水平的细胞因子IL-8；吸引中性粒细胞使系留的β2整合素表达增加75%-100%。在黑色素瘤细胞上的细胞间黏附分子-1和中性粒细胞上的β2整合素相互作用下，促进锚定到血管内皮上。黑色素瘤细胞分泌的IL-8减少，降低了细胞外水平20%-50%，中性粒细胞上的β2整合素降低到50%，使中性粒细胞介导的外渗减少至25%-60%，导致50%不到的黑色素瘤细胞被系留到内皮，留存在肺内。因此，跨内皮运动和肺转移进展减少至50%，显示了靶定黑色素瘤细胞的IL-8具有通过打破中性粒细胞相互作用，降低转移进展的潜能。Cancer Res; 70(14); 6071–82. ©2010 AACR.
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作者:admin@医学,生命科学 2011-01-10 11:02
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