title: Macrophage Infiltration Induces Gastric Cancer Invasiveness by Activating the β-Catenin Pathway.
abstract: BACKGROUND
  Despite evidence that activated macrophages act in an inflammatory microenvironment to promote gastric tumorigenesis via β-catenin signaling, the effects of β-catenin signaling on gastric cancer cell metastasis and the relationship of these cells with surrounding tumor associated macrophages have not been directly studied.
  
  
  METHODS
  Immunohistochemical staining was employed to analyze 103 patients. An invasion assay was used to evaluate the relationship between macrophages and gastric cancer cells. β-catenin gain-of-function and loss-of-function approaches were performed. To assess the β-catenin regulation mechanism in gastric cancer cells, Western blotting and reverse-transcription polymerase chain reaction were used.
  
  
  RESULTS
  Increased density of macrophages was associated with advanced stage and poor survival. Gastric cancer cell lines co-cultured with macrophages conditioned medium showed increased nuclear accumulation of β-catenin and increased invading ability. AKT but not ERK regulated β-catenin translocation. MMP7 and CD44, both β-catenin downstream genes, were involved in macrophage-activated gastric cancer cell invasion.
  
  
  CONCLUSIONS
  Collectively, the clinical data suggest that macrophage infiltration is correlated with increased grade and poor prognosis for gastric cancer patients who underwent radical resection. Macrophages may induce invasiveness by activating the β-catenin pathway.
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ming-Hsun
authors.initials: MH
authors.lastname: Wu
authors.affiliation: Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Jiunn
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Kuo-Tai
authors.initials: KT
authors.lastname: Hua
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Education & Bioethics, Graduate Institute of Medical Education & Bioethics, National Taiwan University College of Medicine, Taiwan.
authors.forename: Ming-Tsan
authors.initials: MT
authors.lastname: Lin
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D021381:Protein Transport; D013274:Stomach Neoplasms / Q000473:pathology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051176:beta Catenin