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  • Title: CXCR4/SDF-1 axis is involved in lymph node metastasis of gastric carcinoma.
    Author: Zhao BC, Wang ZJ, Mao WZ, Ma HC, Han JG, Zhao B, Xu HM.
    Journal: World J Gastroenterol; 2011 May 21; 17(19):2389-96. PubMed ID: 21633638.
    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 immunohistochemistry 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.
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