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Clinical Cancer Research Vol. 9, 3406-3412, August 2003
© 2003 American Association for Cancer Research

Molecular Oncology, Markers, Clinical Correlates

Association of CC Chemokine Receptor 7 with Lymph Node Metastasis of Esophageal Squamous Cell Carcinoma1

Yongzeng Ding, Yutaka Shimada2, Masato Maeda, Atsushi Kawabe, Junichi Kaganoi, Izumi Komoto, Yosuke Hashimoto, Masayuki Miyake, Hiroki Hashida and Masayuki Imamura

Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto 606-8507 [Y. D., Y. S., M. M., A. K., J. K., I. K., Y. H., M. I.], and Department V of Oncology and Department of Thoracic Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka 530-8480 [M. M., H. H.], Japan

Purpose: CC chemokine receptor 7 (CCR7) plays a critical role in the migration of activated dendritic cells to regional lymph nodes. Recent studies have shown that CCR7 is involved in metastasis in some malignant diseases. The role of CCR7 in esophageal squamous cell carcinoma (SCC) has not yet been clarified.

Experimental Design: We performed reverse transcription-PCR analysis for CCR7 in 20 esophageal SCC cell lines and immunohistochemical analysis of 96 esophageal SCC samples. We then performed a cell migration assay, F-actin polymerization, and a phagokinetic assay on esophageal SCC cell lines in the presence of CCL21, a ligand of CCR7.

Results: CCR7 mRNA was detected in 9 of 20 esophageal SCC cell lines. Immunoreactive CCR7 was found mainly in esophageal cancer cells. High CCR7 expression was significantly correlated with esophageal SCC lymphatic permeation, lymph node metastasis, tumor depth, and tumor-node-metastasis stage and was associated with poor survival. In vitro studies demonstrated that CCL21 significantly increased the cell migration ability of esophageal SCC cell lines, and pseudopodia formation was induced by CCL21 stimulation. Furthermore, CCL21 markedly enhanced the motility of esophageal carcinoma cell lines by the phagokinetic assay.

Conclusions: The results suggested that the CCR7/CCL21 receptor ligand system may play a role in the lymph node metastasis of esophageal SCC.




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