title: Macrophage coculture enhanced invasion of gastric cancer cells via TGF-β and BMP pathways.
abstract: OBJECTIVE
  Transforming growth factor β (TGF-β) superfamily plays an important role in regulating gastric cancer progression. As previously demonstrated, tumor-associated macrophages (TAMs) promoted the invasion of gastric cancer cells in Matrigel. However, the role of TGF-β superfamily signaling between TAMs and gastric cancer remains unclear.
  
  
  METHODS
  Three-dimensional dynamic migration imaging system was used to detect gastric cancer invasion rate cocultured with macrophages in Matrigel before or after TGF-β receptor 1 or bone morphogenic protein (BMP) receptor 1A and 1B inhibition; real-time RT-PCR was used to quantitatively investigate gene expression (TGF-β1, TGF-β2, BMP4, and BMP7, ADAM9, MMP9, TIMP3, VEGF-A, and VEGF-C).
  
  
  RESULTS
  TGF-β1, TGF-β2, BMP4, and BMP7 expressions were increased significantly in macrophages grown with cancer cells as compared to macrophages grown alone. The invasion rate and invasion-related genes expressions of both AGS and Hs-746T gastric cancer cell lines were upregulated by macrophages, although the expression profile was different. Invasion rate and invasion-related genes' expressions of AGS cells cocultured with macrophages were downregulated significantly after TGF-βR1 and BMPR1 inhibition.
  
  
  CONCLUSIONS
  Macrophages associated with tumor might promote gastric cancer cells invasion though enhancing TGF-β/BMPs signal pathway. Inhibiting TGF-β/BMPs signal between TAMs and gastric cancer cells might provide a new therapeutic method of gastric cancer.
authors.affiliation: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, PR, China.
authors.forename: Zhanlong
authors.initials: Z
authors.lastname: Shen
authors.forename: Tuuli
authors.initials: T
authors.lastname: Kauttu
authors.forename: Jian
authors.initials: J
authors.lastname: Cao
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: D055415:Bone Morphogenetic Protein 4 / Q000235:genetics; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D018920:Coculture Techniques / Q000379:methods; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D053781:Transforming Growth Factor beta2 / Q000235:genetics
chemical_list: D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D052005:Bone Morphogenetic Protein Receptors, Type I