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