Chemokines and their receptors are essential for leukocyte trafficking, and are also involved in cancer metastasis to specific organs. Although the migration of tumor cells into the lymph nodes is an important aspect of cancer, the processes involved are poorly understood. Chemokine receptors CCR7 and CXCR3 have been shown to play an important role in tumor cell migration and lymph node metastasis. Therefore, the assessment of chemokine receptor expression on lung adenocarcinomas may improve the prediction of the spread of this carcinoma to the lymph nodes. In this study, we examined the expression and function of these two chemokine receptors (CCR7 and CXCR3) in lung adenocarcinoma. By using flow cytometry, they were detected in all of the lung adenocarcinoma cell lines examined. In the chemotaxis assays, A549 cells exhibited CCL21-induced migration, which was significantly suppressed by neutralizing anti-CCR7 antibody. The CXCL10-induced migration of A549 cells was also significantly suppressed by neutralizing anti-CXCR3 antibody. In clinical lung adenocarcinoma samples, we found the expression of CCR7 and CXCR3 in 65 and 90% cases, respectively, most of which had lymph node metastasis. Importantly, the expression of CCR7 was significantly associated with lymph node metastasis, although the expression of CXCR3 was not. These results suggest that the activation of CCR7 and CXCR3 with their ligands preferentially stimulates lung adenocarcinoma metastasis to the draining lymph nodes.

译文

趋化因子及其受体对于白细胞运输至关重要,并且还参与癌症向特定器官的转移。尽管肿瘤细胞向淋巴结的迁移是癌症的重要方面,但对所涉及的过程知之甚少。趋化因子受体CCR7和CXCR3已被证明在肿瘤细胞迁移和淋巴结转移中起重要作用。因此,评估趋化因子受体在肺腺癌上的表达可能会改善该癌向淋巴结扩散的预测。在这项研究中,我们检查了这两种趋化因子受体 (CCR7和CXCR3) 在肺腺癌中的表达和功能。通过使用流式细胞仪,在所有检查的肺腺癌细胞系中检测到它们。在趋化性测定中,A549细胞表现出CCL21-induced的迁移,其被中和anti-CCR7抗体显著抑制。A549细胞的CXCL10-induced迁移也被中和anti-CXCR3抗体显著抑制。在临床肺腺癌样本中,我们发现CCR7和CXCR3分别在65和90% 例中表达,其中大多数有淋巴结转移。重要的是,CCR7的表达与淋巴结转移显着相关,尽管CXCR3的表达并非如此。这些结果表明,CCR7和CXCR3及其配体的激活优先刺激肺腺癌转移至引流淋巴结。

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