Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. May 21, 2011; 17(19): 2389-2396
Published online May 21, 2011. doi: 10.3748/wjg.v17.i19.2389
CXCR4/SDF-1 axis is involved in lymph node metastasis of gastric carcinoma
Bao-Cheng Zhao, Zhen-Jun Wang, Wei-Zheng Mao, Hua-Chong Ma, Jia-Gang Han, Bo Zhao, Hui-Min Xu
Bao-Cheng Zhao, Zhen-Jun Wang, Hua-Chong Ma, Jia-Gang Han, Bo Zhao, Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
Wei-Zheng Mao, Department of General Surgery, Qingdao Municipal Hospital, Qingdao University Medical College, Qingdao 266071, Shandong Province, China
Hui-Min Xu, Department of General Surgery, Weifang People’s Hospital, Weifang 261041, Shangdong Province, China
Author contributions: Zhao BC and Wang ZJ contributed equally to this work; Zhao BC, Wang ZJ and Mao WZ designed the research; Zhao BC, Wang ZJ, Ma HC, Han JG, Zhao B and Xu HM performed the research; Zhao BC, Wang ZJ and Mao WZ conducted the statistical analysis and wrote the manuscript.
Supported by The National Natural Science Foundation of China, No. 30772542
Correspondence to: Wei-Zheng Mao, MD, Department of General Surgery, Qingdao Municipal Hospital, Qingdao University Medical College, Qingdao 266071, Shandong Province, China. maoweizheng2010@163.com
Telephone: +86-532-88905698 Fax: +86-532-85968434
Received: August 19, 2010
Revised: November 13, 2010
Accepted: November 20, 2010
Published online: May 21, 2011
Abstract

AIM: To investigate the role of CXC chemokine receptor-4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) in lymph node metastasis of gastric carcinoma.

METHODS: In 40 cases of gastric cancer, expression of CXCR4 mRNA in cancer and normal mucous membrane and SDF-1 mRNA in lymph nodes around the stomach was detected using quantitative polymerase chain reaction (PCR) (TaqMan) and immunohistochemistric assay. SGC-7901 and MGC80-3 cancer cells were used to investigate the effect of SDF-1 on cell proliferation and migration.

RESULTS: Quantitative reverse transcription PCR and immunohistochemistry revealed that the expression level of CXCR4 in gastric cancer was significantly higher than that in normal mucous membrane (1.6244 ± 1.3801 vs 1.0715 ± 0.5243, P < 0.05). The expression level of CXCR4 mRNA in gastric cancer with lymph node metastasis was also significantly higher than that without lymph node metastasis (0.823 ± 0.551 vs 0.392 ± 0.338, P < 0.05). CXCR4 expression was significantly related to poorly differentiated, high tumor stage and lymph node metastasis. Significant differences in the expression level of SDF-1 mRNA were found between lymph nodes in metastatic gastric cancer and normal nodes (0.5432 ± 0.4907 vs 0.2640 ± 0.2601, P < 0.05). The positive expression of SDF-1 mRNA in lymph nodes of metastatic gastric cancer was consistent with the positive expression of CXCR4 mRNA in gastric cancer (r = 0.776, P < 0.01). Additionally, human gastric cancer cell lines expressed CXCR4 and showed vigorous proliferation and migratory responses to SDF-1. AMD3100 (a specific CXCR4 antagonist) was also found to effectively reduce the migration of gastric cancer cells.

CONCLUSION: The CXCR4/SDF-1 axis is involved in the lymph node metastasis of gastric cancer. CXCR4 is considered as a potential therapeutic target in the treatment of gastric cancer.

Keywords: Gastric carcinoma; Chemokines; Stromal cell-derived factor-1; CXC chemokine receptor-4; Lymph node metastasis