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Fibulin-5 is a tumour suppressor inhibiting cell migration and invasion in ovarian cancer
  1. Jin Hyung Heo1,
  2. Ji-ye Song2,
  3. Ju-yeong Jeong2,
  4. Gwangil Kim1,2,
  5. Tae Heon Kim1,2,
  6. Haeyoun Kang1,
  7. Ah-young Kwon1,
  8. Hee Jung An1,2
  1. 1Department of Pathology, CHA Bundang Medical Center, CHA University, Sungnam, Korea
  2. 2Clinical Research Institute, CHA Bundang Medical Center, CHA University, Sungnam, Korea
  1. Correspondence to Dr Hee Jung An, Department of Pathology, CHA Bundang Medical Center, CHA University, 351 Yatap-dong, Bundang-gu, Sungnam-si, Gyeonggi-do 463-712, Korea; hjahn{at}cha.ac.kr

Abstract

Aims 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.

  • CANCER RESEARCH
  • EXTRACELLULAR MATRIX
  • OVARIAN TUMOUR

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