title: [The role of CXCR4 in lung cancer metastasis and its possible mechanism].
abstract: OBJECTIVE
  To investigate the role of CXCR4 in the metastasis of human lung cancer and its possible mechanism.
  
  
  METHODS
  Lung cancer cells of the lines 95C and 95D with high or low metastatic potential were transfeted with CXCR4 antisense plasmid pcDNA-ASX4, whole length eukaryotic expression plasmid pcDNA-CXCR4 (95D-ASX4 and 95C-X4 cell lines), and corresponding plasmid pcDNA3 (95C-pC and 95D-pC cell lines). 95C, 95C-pC, 95C-X4, 95D, and 95D-pC cells were injected subcutaneously into Balb/c nu/nu mice, 4 approximately 5 mice in a group. The mice were observed twice a week. Ten weeks later the mice were killed and the tumor in situ and the lungs were taken out to undergo histological examination. The effect of CXCR4 expression on the cell migration, MMP-2 activity, adhesion and GRO-a expression of lung cancer cells were detected by chemotaxis and chemoinvasion assay, zymography, adhesion assay and RT-PCR respectively. The polymerization of F-actin was measured by FACS and confocal microcopy. Western blotting was used to detect the phospharylation of ERK1/2 in 85D cells
  
  
  RESULTS
  Metastasis was not found in the mice injected with 95C and 95C-pC cells, and was seen in 2/5 of the mice injected with 95C-X4 cells, 3/4 of the mice injected with 95D and 95D-pC cells, 2/5 of the mice injected with 95D-ASX4 cells, however, the number of metastatic nodes in the lungs of 95D-ASX4 group was significantly less than those in the 95D and 95D-pC groups (P = 0.044). SDF-1a, a CXCR4 specific ligand, induced the migratory response and F-actin polymerization in the lung cancer cells; SDF-1a promoted the MMP-2 activity, the adhesion to vascular endothelial cells and GRO-a expression; and neutralizing CXCR4 antibody inhibited these effects to some degree. Moreover, SDF-1a induced the phosphorylation of ERK1/2 in human lung cancer cells.
  
  
  CONCLUSIONS
  Metastasis of human lung cancer depends on, to some degree, the interaction of CXCR4 and SDF-1 that are involved in this process by regulating the active locomotion, MMP-2 activity, adhesion ability or GRO-a expression.
authors: Department of Immunology, Shanghai Medical College of Fudan University, Shanghai 20032, China.
authors: Li-ping
authors: LP
authors: Su
authors: Jin-ping
authors: JP
authors: Zhang
authors: Huan-bin
authors: HB
authors: Xu
authors: Jin
authors: J
authors: Chen
authors: Ying
authors: Y
authors: Wang
authors: Si-dong
authors: SD
authors: Xiong
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4; D020778:Matrix Metalloproteinase 2