title: Protumoral effect of macrophage through Axl activation on  mucoepidermoid carcinoma.
abstract: OBJECTIVE
  This study aims to test the potential involvement of Axl signaling in the protumoral effect of tumor-associated macrophages (TAMs) in mucoepidermoid carcinoma (MEC).
  
  
  METHODS
  We carried out cocultured experiments by incubation of MEC cells (UTMUC-1) and macrophages (THP-1) and examined Axl activation status. The expression of MMPs and behavior change were examined in UT-MUC-1 cells. The effect of Axl signaling on co-cultured cancer cells was further investigated by knockdown Axl expression and suppression by Axl-specific inhibitor R428.
  
  
  RESULTS
  Activation of Axl signaling and increased expression and activity of MMP-2 and MMP-9 along with increased invasion/migration ability in MEC cells were observed when co-cultured with TAMs. Upon knockdown of Axl in MEC or addition of R428 in the co-cultured system, these co-cultured effects were diminished.
  
  
  CONCLUSIONS
  TAMs play a protumoral role in MEC via activation of the Axl signaling pathway, up-regulating MMPs expression, and increasing invasion/migration ability.
authors.forename: Kuo-Chou
authors.initials: KC
authors.lastname: Chiu
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Lee
authors.forename: Shyun-Yeu
authors.initials: SY
authors.lastname: Liu
authors.forename: Chi-Tai
authors.initials: CT
authors.lastname: Yeh
authors.forename: Ren-Yeong
authors.initials: RY
authors.lastname: Huang
authors.forename: Da-Yo
authors.initials: DY
authors.lastname: Yuh
authors.forename: Jen-Chan
authors.initials: JC
authors.lastname: Cheng
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chou
authors.forename: Yi-Shing
authors.initials: YS
authors.lastname: Shieh
mesh_terms: D001567:Benzocycloheptenes / Q000494:pharmacology; D018277:Carcinoma, Mucoepidermoid / Q000201:enzymology* / Q000473:pathology; D018929:Cell Culture Techniques; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018920:Coculture Techniques; D018450:Disease Progression; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D008262:Macrophage Activation / Q000502:physiology; D008264:Macrophages / Q000201:enzymology*; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D009361:Neoplasm Invasiveness; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014230:Triazoles / Q000494:pharmacology; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D001567:Benzocycloheptenes; D011518:Proto-Oncogene Proteins; D014230:Triazoles; C548378:bemcentinib; D020794:Receptor Protein-Tyrosine Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human