title: Fibulin-5 is a tumour suppressor inhibiting cell migration and invasion in ovarian cancer.
abstract: OBJECTIVE
  Fibulin-5 is an extracellular matrix (ECM) glycoprotein which has a role in the organisation and stabilisation of ECM structures and regulating cell proliferation and tumourigenesis. Here, the expression of fibulin-5 and its functional effects on the migration and invasion of ovarian cancer cells were assessed.
  
  
  METHODS
  Expression of fibulin-5 was detected in 44 ovarian tumour tissues by qRT-PCR, Western blotting and immunohistochemistry. We performed cell migration and invasion assays, and cell cycle analysis in fibulin-5 transfected SKOV3 (SKOV3-FBLN5) cells and the parental SKOV3 cells. We further examined the expression of three tissue inhibitors of metalloproteinases (TIMPs) and seven matrix metalloproteinases (MMPs) by RT-PCR.
  
  
  RESULTS
  mRNA and protein expression of fibulin-5 were down-regulated (0.05-fold and 0.1-fold) in ovarian carcinomas compared with control tissues (p<0.01 and p=0.022). In wound-healing and invasion assays, significantly fewer SKOV3-FBLN5 cells than SKOV3 control cells migrated and invaded (39.1%, p=0.046 and 70%, p=0.03, respectively), which was reversed by siRNA-treatment. Overexpression of fibulin-5 induced G2/M arrest and increased cyclin B1, CDC2 and CDC25C. Expression of TIMP-2 (0.56-fold), MMP-3 (0.43-fold) and MMP-13 (0.18-fold) was lower and MMP-9 expression (2.20-fold) was higher in SKOV3-FBLN5 cells than in control cells.
  
  
  CONCLUSIONS
  Fibulin-5 is significantly down-regulated in ovarian carcinoma and acts as a tumour suppressor by inhibiting the migration and invasion of ovarian cancer cells.
authors.affiliation: Department of Pathology, CHA Bundang Medical Center, CHA University, Sungnam, Korea.
authors.forename: Jin Hyung
authors.initials: JH
authors.lastname: Heo
authors.affiliation: Clinical Research Institute, CHA Bundang Medical Center, CHA University, Sungnam, Korea.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Song
authors.affiliation: Clinical Research Institute, CHA Bundang Medical Center, CHA University, Sungnam, Korea.
authors.forename: Ju-Yeong
authors.initials: JY
authors.lastname: Jeong
authors.affiliation: Department of Pathology, CHA Bundang Medical Center, CHA University, Sungnam, Korea Clinical Research Institute, CHA Bundang Medical Center, CHA University, Sungnam, Korea.
authors.forename: Gwangil
authors.initials: G
authors.lastname: Kim
authors.affiliation: Department of Pathology, CHA Bundang Medical Center, CHA University, Sungnam, Korea Clinical Research Institute, CHA Bundang Medical Center, CHA University, Sungnam, Korea.
authors.forename: Tae Heon
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Pathology, CHA Bundang Medical Center, CHA University, Sungnam, Korea.
authors.forename: Haeyoun
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Pathology, CHA Bundang Medical Center, CHA University, Sungnam, Korea.
authors.forename: Ah-Young
authors.initials: AY
authors.lastname: Kwon
authors.affiliation: Department of Pathology, CHA Bundang Medical Center, CHA University, Sungnam, Korea Clinical Research Institute, CHA Bundang Medical Center, CHA University, Sungnam, Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: An
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; D012333:RNA, Messenger; C560823:TIMP2 protein, human; D025521:Tumor Suppressor Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D053505:Matrix Metalloproteinases, Secreted
keywords: CANCER RESEARCH; EXTRACELLULAR MATRIX; OVARIAN TUMOUR