Poster Presentation 29th Lorne Cancer Conference 2017

Targeting tumour vascularisation to control breast cancer progression. (#124)

Emma Thompson 1 , Gelareh Farshid 2 3 , Yeesim Khew-Goodall 1 4 , Geoffrey Lindeman 5 , Angel Lopez 1 3 , Claudine Bonder 1 3
  1. Centre for Cancer Biology, University of South Australia & SA Pathology, Adelaide
  2. BreastScreenSA, Adelaide
  3. Adelaide Medical School, Faculty of Health Sciences, University of Adelaide., Adelaide
  4. School of Biological Sciences, University of Adelaide, Adelaide
  5. Walter and Eliza Hall Institute for Medical Research, Melbourne

Tumour vascularisation underpins the growth and metastasis of all solid cancers with richly vascularised tumours indicative of highly invasive & aggressive breast cancers and correlating with reduced patient survival. Tumour vascularisation can occur through endothelial cell (EC)-dependent mechanisms (angiogenesis) or an EC-independent mechanism; vasculogenic mimicry (VM). Vasculogenic mimicry is the process whereby tumour cells themselves align into rudimentary vascular networks to gain access to oxygen and nutrients for tumour growth. Increasing evidence suggests that interleukin-3 (IL-3) is involved in several human pathologies, notably cancer where levels of IL-3 receptor (IL-3R) expression correlate clinically with reduced patient survival. We propose that IL-3 as a key regulatory factor in breast cancer that mediates angiogenesis as well as VM and thus promotes breast cancer progression. We have new data to show that IL-3R specific antibodies block VM formation of breast cancer cell lines in vitro. Moreover, in an in vivo study of breast cancer progression, NOD/SCID mice containing the human invasive breast cancer cell line MDA-MB-231-LM2 showed reduced tumour size when treated with IL-3R blocking antibodies. Human patient samples also suggest that IL-3 is being produced by the breast cancer directly. We therefore hypothesise that IL-3 represents an underappreciated factor in the progression of breast cancer and by targeting the IL-3/IL-3R axis with our IL-3R specific antibodies we will develop a new treatment option for breast cancer patients that, for the first time, targets both the EC-dependent and VM components of breast cancer progression.