Poster Presentation 28th Lorne Cancer Conference 2016

mTORC signalling is required for the proliferation of non-small cell lung cancer (#224)

Andrew Carey 1 2 , Rowena Lewis 1 2 , Marie-Liesse Asselin-Labat 3 , Nicole Kountouri 1 2 , Matthias Ernst 1 2 , Robert JJ O'Donoghue 1 2
  1. School of Cancer Medicine, La Trobe University, Bundoora, Victoria, Australia
  2. Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
  3. Stem Cells and Cancer Division, Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia

Lung cancer is the leading cause of cancer related deaths worldwide. Inflammation, due to tobacco use or lung disease, is a common predisposing factor for the development of lung cancer. The IL-6, and the related cytokine IL-11, are elevated during inflammation and have been implicated in the progression of many cancers, including colorectal and gastric cancers. We assessed the activity of IL-6/11 in human non-small cell lung cancer (NSCLC) and the therapeutic potential of inhibiting their activity. QRT-PCR and western blotting were used characterise the expression and activation of IL-6/11 signalling pathway in human NSCLC cell lines (A549, H358, H1650, H1975, SKLU1). MTS assays were performed to assess the effects of IL-6/11 stimulation, or AZD1480, INC424, or Tocilizumab on proliferation. All NSCLC cell lines expressed genes required for IL-6/11 signalling. Notably, IL11 could not be detected by qRT-PCR. Levels of phosphorylated rpS6K (prpS6K), a marker of mTORC activation, were consistent across cell lines. However, levels of STAT3 and ERK1/2 phosphorylation were highly variable between cell lines. A549 cells were the only cell line to show a mild increase in proliferation following IL-6/IL-11 stimulation. Yet, both AZD1480 and RAD001 were capable of inhibiting growth of NSCLC cells in vitro and tumour growth in vivo. The IL-6/11 signalling pathways are activated in NSCLC cells and inhibition of the downstream mTORC pathway is effective in impeding their proliferation. Furthermore, data from NSCLC tumours and lines implicate the tumour associated stroma as a source of IL-6/11 during tumour progression.