Poster Presentation 9th GeneMappers Conference 2012

HSPGs and human breast cancer cell proliferation (#120)

Rachel M Okolicsanyi 1 , Lyn R Griffiths 1 , Larisa M Haupt 1
  1. Griffith University, Southport, Qld, Australia

Heparan sulfate proteoglycans (HSPGs) are key components of the ECM (extracellular matrix) and are known to influence cell proliferation, invasion and cellular signalling. Here, we examine the influence of HSPGs, including side chain modification enzymes and core proteins, on MDA-MD-231 and MCF-7 human breast cancer (HBC) cells during in vitro proliferation (D1, D3 and D5). Clear differences were observed between the two cell types that may be of relevance to tumours in vivo. Addition of the HS agonist heparin to the cultures predictably increased chain initiation and modification enzymes, including EXT1 (MCF-7; p=0.0002, D1 inc; MDA p=1.77x1e-8, D3 inc) and NDST1 (MCF-7 p=0.016, D1 inc; MDA p=3.31x1e-5, D3 inc). Significant changes were also observed in core protein gene expression including SDC1 (MCF-7 p=0.02, D1 inc; MDA p=0.011, D3 dec) and GPC6 (MCF-7 p=1.6x1e-7, D3 inc; MDA p=2.94x1e-9, D3 inc). Wnt genes upregulated at D5 in MDA-MB-231 cells included AXIN1, 9 fold inc, p=1.4x1e-5; WNT4A, 15 fold inc, p=0.006; MYC, 6 fold inc, p=0.0003. The significant gene expression changes observed within HS chain initiation and modification enzymes, core proteins, and key Wnt pathway signalling molecules support a role for HSPGs in cellular proliferation in breast cancers. Enhanced proliferation of tumour cells is a key aspect of a tumours ability to proceed to localised invasion and subsequent metastasis. We are currently expanding this work to further examine HSPGs along the invasive and metastatic cascade.