Mashino Kohjiro, Sadanaga Noriaki, Yamaguchi Hiroshi, Tanaka Fumiaki, Ohta Mitsuhiko, Shibuta Kenji, Inoue Hiroshi, Mori Masaki
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumibaru, Beppu 874-0838, Japan.
Cancer Res. 2002 May 15;62(10):2937-41.
The interactions of chemokine receptor CCR7 and its ligands are essential for migration of lymphocytes and dendritic cells to lymph nodes. In this study, we found that 4 of 6 (67%) gastric carcinoma cell lines tested expressed functional CCR7 for the chemokine CCL21/6Ckine, as demonstrated by calcium mobilization and actin polymerization assays. Moreover, we also showed that signaling through CCR7 induced chemotactic and invasive responses in CCR7-positive gastric carcinoma cells. In clinical samples, immunohistochemical assay showed that CCR7-positive carcinoma cells were detected in 42 of 64 (66%) cases and a significant difference in both lymph node metastasis (P < 0.001) and lymphatic invasion (P < 0.001) between CCR7-positive and -negative cases. Patients with CCR7-positive tumors had a significantly poorer prognosis than those with CCR7-negative tumors (P < 0.05). Stepwise regression analysis revealed that the most important factor related to lymph node metastasis was the expression of CCR7. These results indicated that CCR7 and its ligands interaction is associated with preferential lymph node metastasis of gastric carcinoma.
趋化因子受体CCR7与其配体的相互作用对于淋巴细胞和树突状细胞向淋巴结迁移至关重要。在本研究中，我们发现，通过钙动员和肌动蛋白聚合分析表明，所检测的6种胃癌细胞系中有4种（67%）表达针对趋化因子CCL21/6Ckine的功能性CCR7。此外，我们还表明，通过CCR7的信号传导在CCR7阳性胃癌细胞中诱导趋化和侵袭反应。在临床样本中，免疫组织化学分析显示，64例中有42例（66%）检测到CCR7阳性癌细胞，CCR7阳性和阴性病例在淋巴结转移（P < 0.001）和淋巴管浸润（P < 0.001）方面均存在显著差异。CCR7阳性肿瘤患者的预后明显比CCR7阴性肿瘤患者差（P < 0.05）。逐步回归分析显示，与淋巴结转移相关的最重要因素是CCR7的表达。这些结果表明，CCR7及其配体的相互作用与胃癌的优先淋巴结转移有关。
