title: Role of toll-like receptor 4 on the immune escape of human oral squamous cell carcinoma and resistance of cisplatin-induced apoptosis.
abstract: BACKGROUND
  Toll-like receptor 4 (TLR4) is expressed on immune cells as a sensor that recognizes lipopolysaccharide (LPS), a microbial conserved component. It has recently been determined that the expression of TLR4 is also found in various types of tumor cells. Cisplatin is a widely used chemotherapeutic agent for oral squamous cell carcinoma (OSCC) treatment. However, the mechanisms responsible for cisplatin resistance are not well understood.
  
  
  RESULTS
  The present study was designed to elucidate the role of TLR4 expression in human OSCC regarding immune escape and apoptotic resistance to cisplatin. TLR4 and the myeloid differentiation primary response gene 88 (MyD88) were highly expressed in OSCC cell lines. Upon LPS stimulation both NF-κB and p38 MAPK pathways were activated in OSCC cell lines, followed by the production of large quantities of IL-6, IL-8 and VEGF compared with human immortalized oral epithelia cells (HIOECs). OSCC cell lines were found to be resistant to cisplatin-mediated apoptosis after pretreatment with LPS.
  
  
  CONCLUSIONS
  Our results suggested that TLR4 was functionally expressed in human OSCC cells and development of resistance to cisplatin in human OSCC might occur through the mechanism involving TLR4 and its signaling pathway. Suppression of TLR4 and its signaling pathway might thus elevate sensitivity to cisplatin and potentially help improve the prognosis of patients with OSCC.
authors.affiliation: Department of Clinical Laboratories, Ninth People's Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai 200011, China.
authors.forename: Zujun
authors.initials: Z
authors.lastname: Sun
authors.forename: Qingqiong
authors.initials: Q
authors.lastname: Luo
authors.forename: Dongxia
authors.initials: D
authors.lastname: Ye
authors.forename: Wantao
authors.initials: W
authors.lastname: Chen
authors.forename: Fuxiang
authors.initials: F
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D009062:Mouth Neoplasms / Q000235:genetics* / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism; D019139:Tumor Escape / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D042461:Vascular Endothelial Growth Factor A; D048051:p38 Mitogen-Activated Protein Kinases; D002945:Cisplatin