title: IL10, IL11, IL18 are differently expressed in CD14+ TAMs and play different role in regulating the invasion of gastric cancer cells under hypoxia.
abstract: BACKGROUND
  Recent evidence shows that chronic inflammation mediated by tumor-associated macrophage (TAM) play an important role in malignant tumor formation and progression. Interleukins expressed in TAMs regulate this progress. Hypoxia is a salient feature of solid tumors and has a profound influence on the biology of TAMs However, the role of interleukins in the gastric cancer progression under hypoxia is not clear.
  
  
  METHODS
  Realtime RT-PCR was used to quantitatively investigate the IL10, IL11 and IL18 expression in CD14(-) normal macrophages and CD14(+) TAMs co-cultured with four gastric cancer cell lines including non-metastatic cell line AGS and metastatic cell lines HGC-27, Hs-746T and NCI-N87 under normal or hypoxic conditions. In addition, the correlation between IL10, IL11, IL18 expression in TAMs under hypoxia and mobility of gastric cancer cells were analyzed.
  
  
  RESULTS
  Under normal conditions, the IL10 and IL18 expressions were significantly higher in CD14(+) TAMs co-cultured with non-metastatic cell line than with metastatic cell lines. IL11 expression was significantly higher in CD14(+) TAMs co-cultured with distant metastasis cell lines. Hypoxia induced IL10, IL11 and IL18 expression up regulated significantly in TAMs co-cultured with AGS, Hs-746T and NCI-N87 cell line. There was a significant negative correlation between IL11 expression in CD14(+) TAMs and gastric cancer cell invasion speed under hypoxic conditions (r=0.861, P<0.001).
  
  
  CONCLUSIONS
  The up-regulation of IL10, IL11 and IL18 expression in TAMs by hypoxia differed in gastric cancer cell lines. IL11 expression in TAMs might play more important role than IL10 and IL18 expression in regulating the invasion of gastric cancer cells under hypoxia.
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, PR China. Shenlong1977@163.com
authors.forename: Zhanlong
authors.initials: Z
authors.lastname: Shen
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: D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D018920:Coculture Techniques; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D017370:Interleukin-11 / Q000235:genetics / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology*
chemical_list: D017370:Interleukin-11; D020382:Interleukin-18; D007378:Interleukins; D018950:Lipopolysaccharide Receptors; D016753:Interleukin-10