title: The impact of EPLINα (Epithelial protein lost in neoplasm) on endothelial cells, angiogenesis and tumorigenesis.
abstract: BACKGROUND
  EPLIN (epithelial protein lost in neoplasm) is a cytoskeletal associated protein involved in the regulation of actin dynamics and subsequently in cell motility. EPLIN expression is frequently reduced in a variety of cancer cells and tissues and this loss may account for increased invasive traits in cancer cells. The current study aimed to assess the role of EPLIN in endothelial cells and the angiogenic process.
  
  
  METHODS
  EPLINα expression was enhanced in HECV endothelial cells through transfection with a pEF6 expression plasmid containing the full coding sequence of EPLINα. The impact of EPLINα on HECV cells was then assessed using a range of in vitro and in vivo models.
  
  
  RESULTS
  transfection and over-expression of HECV cells with EPLINα expression plasmid resulted in a significant reduction in cell-matrix adhesion (P = 0.003), the rate of migration (P = 0.009) and tubule formation (P = 0.007) and also enhanced paxillin staining compared to transfection controls. Additionally, MDA-MB-231 breast cancer cells co-injected with HECV(EPLIN exp) cells developed at a slower rate than those co-injected with HECV(pEF6) cells (day 26, P = 0.05; day 33, P = 0.065, overall deviation over time P < 0.001). Treatment of HECV(EPLIN exp) cells with ERK inhibitor could rescue HECV cells from the inhibitory effect of EPLINα over-expression on tubule formation, returning these cells to control levels.
  
  
  CONCLUSIONS
  EPLINα over-expression can regulate HECV cell motility, matrix adhesion and tubule formation in vitro and slow in vivo tumour formation, suggesting an anti-angiogenic role for EPLINα. Extracellular signal-regulated kinase (ERK) also appears to be linked to the ability of EPLINα to inhibit tubule formation in vitro.
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Cardiff CF14 4XN, UK. sandersaj1@cf.ac.uk
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sanders
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D020533:Angiogenesis Inhibitors; D003598:Cytoskeletal Proteins; C403263:LIMA1 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases