title: Polarization of tumor-associated macrophages and Gas6/Axl signaling in oral squamous cell carcinoma.
abstract: BACKGROUND
  This study investigated the potential involvement of Axl signaling in polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC).
  
  
  METHODS
  Condition medium (CM) from OSCC cells (OEC-M1 and YD38) were collected and their effects on macrophage (THP-1) polarization were examined. Modulation of Axl, PI3/Akt, and NF-κB were performed to investigate their potential involvement in TAM polarization. Expression of pAxl and CD206 were analyzed by immunohistochemistry in OSCC tissues.
  
  
  RESULTS
  THP-1 polarized to M2 phenotype with increasing expression of interleukins, vascular endothelial growth factor, matrix metalloproteinase and CD206 upon treatment with CM of OSCC. Activated Axl signaling in OSCC enhanced M2 induction ability. Suppression of Axl signaling and inhibition of PI3/Akt and NF-κB diminished M2 induction. pAxl expression was significantly associated with distribution of CD206 positive cells in OSCC tissues.
  
  
  CONCLUSIONS
  Axl signaling of OSCC involved in polarizing TAMs toward M2 phenotype. Induction of M2 phenotype macrophage polarization by OSCC cells might involve the Axl/PI3/Akt/NF-κB pathway.
authors.affiliation: Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan; Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Kuo-Chou
authors.initials: KC
authors.lastname: Chiu
authors.affiliation: Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Oral & Maxillofacial Surgery, ChiMei Medical Center, Tainan, Taiwan.
authors.forename: Shyun-Yeu
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chou
authors.affiliation: Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ren-Yeong
authors.initials: RY
authors.lastname: Huang
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shih-Ming
authors.initials: SM
authors.lastname: Huang
authors.affiliation: Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan. Electronic address: ndmcyss@mail.ndmctsgh.edu.tw.
authors.forename: Yi-Shing
authors.initials: YS
authors.lastname: Shieh
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D007378:Interleukins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; D020794:Receptor Protein-Tyrosine Kinases; D020782:Matrix Metalloproteinases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human
keywords: Axl; Microenvironment; Oral squamous cell carcinoma; Tumor-associated macrophage