PRS PSRC Podium Proofs 2016
Anne C. O’Neill, MBBCh, PhD, Pardeep Agarwaal, PhD, Armand Keating, MD, Stefan OP Hofer, MD, PhD
From the University Health Network University of Toronto, Toronto, ON, Canada
PURPOSE: Stem cell-based reconstructive techniques offer minimally invasive options for autologous breast reconstruction, but there are concerns regarding their oncological safety in cancer patients. In this study, we investigate whether pretreatment of human adipose-derived stem cells (ASCs) could induce apoptosis in breast cancer cells and therefore confer oncological benefits in reconstruction.
METHODS: ASCs were isolated from human abdominal fat and expanded in vitro. ASCs were exposed to interferon (IFN)-γ in culture for 72 hours. The effect of IFN-γ exposure on TRAIL expression was determined. The mesenchymal triple negative breast cancer cell line MDA-MB-231 was cocultured with IFN-γ-treated ASCs for 72 hours. The effect on MDA-MB-231 cell survival was determined.
RESULTS: Untreated ASCs did not express TRAIL. Exposure to IFN-γ induced TRAIL expression in ASCs in a dose-dependent manner. Coculture of IFN-γ-treated ASCs with the MDA-MB-231 cell line resulted in significant apoptosis of cancer cells. Untreated ASCs did not significantly alter MDA-MB-231 proliferation rates. The presence of TRAIL death receptors (DR1/DR2) on MDA-MB-231 breast cancer cells was confirmed. Inhibition of TRAIL reversed the apoptotic effect of IFN-γ-treated ASCs. Upregulation of caspase 3/7 confirmed apoptotic cell death
CONCLUSIONS: Pretreatment of ASCs with IFN-γ induces TRAIL expression resulting in apoptosis of the mesenchymal triple negative MDA-MB-231 breast cancer cell line. IFN-γ treatment of ASCs may confer oncological benefits and improve the safety of stem cell-based reconstructive strategies in patients with TRAIL sensitive tumor types.