title: CXCR4/SDF-1 axis is involved in lymph node metastasis of gastric carcinoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Bao-Cheng
authors.initials: BC
authors.lastname: Zhao
authors.forename: Zhen-Jun
authors.initials: ZJ
authors.lastname: Wang
authors.forename: Wei-Zheng
authors.initials: WZ
authors.lastname: Mao
authors.forename: Hua-Chong
authors.initials: HC
authors.lastname: Ma
authors.forename: Jia-Gang
authors.initials: JG
authors.lastname: Han
authors.forename: Bo
authors.initials: B
authors.lastname: Zhao
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Xu
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D001596:Benzylamines; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000080027:Cyclams; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D015398:Signal Transduction / Q000502:physiology*; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
chemical_list: D001596:Benzylamines; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D012333:RNA, Messenger; D019718:Receptors, CXCR4; C088327:plerixafor