Poster Presentation 26th Lorne Cancer Conference 2014

ABCA1 promotes aggressive characteristics in epithelial ovarian cancer (#280)

Rebekka Williams 1 , Amanda Russell 1 , Angelika Bongers 1 , Claudia Flemming 1 , Wendy Jessup 2 , Anna DeFazio , Georgia Chenevix-Trench 3 , Michelle Haber 1 , Murray Norris 1 , Michelle Henderson 1
  1. CCIA, Randwick, NSW, Australia
  2. Atherosclerosis Laboratory, ANZAC Research Institute, Concord, NSW, Australia
  3. Queensland Institute of Medical Research, Brisbane, Queensland, Australia

Background
The survival rates for epithelial ovarian cancer (EOC) are very poor and have seen little improvement over the past few decades. Our recent work highlighted the ABCA transporter family, specifically expression of the ABCA1 cholesterol transporter, to be associated with poor outcome (1). Follow up analysis also identified high-level expression of ABCA1 correlated with high grade serous tumours displaying prominent desmoplastic characteristics (1,2). This study aims to determine whether high ABCA1 protein levels influence EOC progression through the promotion of key aggressive characteristics.
Methods
The cell lines, Skov3, Hey and 27/87, were selected from a panel of EOC cell lines based on their comparatively high level of ABCA1 protein expression as determined by western blot. The impact of siRNA-mediated gene suppression of ABCA1 was assessed by colony formation, growth and migration assays. Migration ability was measured in both wound healing and transwell assays.
Results
Suppression of ABCA1 by each of three independent siRNA oligonucleotides resulted in reduced colony forming ability in each of the three cell lines. While ABCA1 knockdown appeared to have little impact on migration of Skov3 cells, migration was significantly reduced in 27/87 and Hey cells in response to ABCA1 knockdown.
Conclusions
Results to date suggest that ABCA1 is involved in promoting a more aggressive EOC phenotype in some ovarian cancer cell types. Further investigation is required to determine the mechanisms by which ABCA1 may influence ovarian cancer growth and migration, such as through microvesicle formation or secretion.

  1. Hedditch, E et al JNCI, under final review.
  2. Tothill et al 2008