title: Soluble HLA-G regulates motility and invasion of the trophoblast-derived cell line SGHPL-4.
abstract: BACKGROUND
  Soluble human leucocyte antigen-G (sHLA-G) is secreted by extravillous trophoblast (EVT) and has roles in regulating immune cells within the decidua. HLA-G expression on EVT increases as they approach uterine spiral arteries and we have suggested that sHLA-G may be important in the remodelling of these vessels. The autocrine role of sHLA-G in regulating trophoblast function at this critical phase has not been studied. We aimed to investigate the effects of sHLA-G on trophoblast motility, invasion and survival.
  
  
  METHODS
  The human EVT line, SGHPL-4, was stably transfected to over-express sHLA-G (SGHPL-4sG1). Motility and apoptosis were assessed by time-lapse microscopy. Cells were cultured on microcarrier beads embedded in fibrin gels to assess invasion. The effect of sHLA-G expression on motility, invasion and apoptosis in response to stimulation with either hepatocyte growth factor (HGF) or epidermal growth factor (EGF) was determined.
  
  
  RESULTS
  There was no difference in the motility of either SGHPL-4 cells or SGHPL-4sG1 cells in the absence of stimulation. However, sHLA-G inhibited HGF-induced EVT motility. HGF- and EGF-induced invasions were significantly inhibited in SGHPL-4sG1 compared with SGHPL-4 cells. Increased expression of HLA-G had no significant effect on tumour necrosis factor (TNF)-alpha/actinomycin-induced apoptosis.
  
  
  CONCLUSIONS
  Growth factor-stimulated trophoblast motility and invasion are regulated by sHLA-G, indicating a novel autocrine role. The inhibition of trophoblast invasion at the spiral artery may be important to allow interactions leading to vascular remodelling.
authors.affiliation: Division of Basic Medical Sciences, Developmental and Endocrine Signalling Centre, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK. j.mccormick@sgul.ac.uk
authors.forename: James
authors.initials: J
authors.lastname: McCormick
authors.forename: Guy St J
authors.initials: GS
authors.lastname: Whitley
authors.forename: Philippe
authors.initials: P
authors.lastname: Le Bouteiller
authors.forename: Judith E
authors.initials: JE
authors.lastname: Cartwright
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D019898:Autocrine Communication / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism*; D059951:HLA-G Antigens; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D011247:Pregnancy; D014162:Transfection; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D014599:Uterus / Q000098:blood supply / Q000166:cytology
chemical_list: D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor