title: Both macrophages and hypoxia play critical role in regulating invasion of gastric cancer in vitro.
abstract: BACKGROUND
  As previously demonstrated, tumor associated macrophages (TAMs) infiltration is associated with some cancers invasion and metastasis. However, the role of TAMs in the gastric cancer remains unclear.
  
  
  METHODS
  Three- dimensional dynamic migration imaging system and real time RT-PCR were used to quantitatively investigate the effect of macrophages on the cancer cell mobility and gene expression related to cancer invasion and metastasis, including ADAM8, ADAM9, MMP9, TIMP3, VEGF-A and IL8 genes, in AGS, HGC-27, Hs-746T and NCI-N87 gastric cancer cell lines under normal or hypoxic conditions.
  
  
  RESULTS
  Under normal conditions, the cancer cell invasion rate was increased significantly and all six gene expressions were upregulated in all four cancer cell lines by macrophages. Under hypoxia the changes in the cancer cell invasion rate induced by macrophages was negatively correlated to the TIMP3 expression. In non- metastatic cell line AGS, the increase in migration rate induced by macrophages was further elevated under hypoxia with increased ADAM8 and ADAM9 expression and decreased MMP9 and TIMP3 expressions. Under hypoxia, the induction by macrophages for IL-8 expression was increased significantly in distant metastatic cell lines NCI-N87 and HS-746T, VEGF-A was increased in HGC-27 cell line.
  
  
  CONCLUSIONS
  Both macrophages and hypoxia play an indispensable role in regulating the invasion of gastric cancer cells in vitro; ADAMs, MMP9 and TIMP3 might be involved in TAM induced invasive power of gastric cancer cells.
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, PR China. shenlong1977@163.com
authors.forename: Zhanlong
authors.initials: Z
authors.lastname: Shen
authors.forename: Tuuli
authors.initials: T
authors.lastname: Kauttu
authors.forename: Hanna
authors.initials: H
authors.lastname: Seppänen
authors.forename: Sanna
authors.initials: S
authors.lastname: Vainionpää
authors.forename: Yingjiang
authors.initials: Y
authors.lastname: Ye
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.forename: Harri
authors.initials: H
authors.lastname: Mustonen
authors.forename: Pauli
authors.initials: P
authors.lastname: Puolakkainen
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D010100:Oxygen / Q000494:pharmacology / Q000502:physiology; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism
chemical_list: D016209:Interleukin-8; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases; D010100:Oxygen