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[Cancer Research 62, 2937-2941, May 15, 2002]
© 2002 American Association for Cancer Research

Tumor Biology

Expression of Chemokine Receptor CCR7 Is Associated with Lymph Node Metastasis of Gastric Carcinoma1

Kohjiro Mashino, Noriaki Sadanaga, Hiroshi Yamaguchi, Fumiaki Tanaka, Mitsuhiko Ohta, Kenji Shibuta, Hiroshi Inoue and Masaki Mori2

Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu 874-0838, Japan

The interactions of chemokine receptor CCR7 and its ligands are essentialfor 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.




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