Stimulation Of Adipose Derived Stem Cells With Interferon Gamma Induces Trail-mediated Apoptosis In Triple Negative Breast Cancer.
Anne C. O'Neill, MBBCh PhD, Pardeep Agarwaal, PhD, Armand Keating, MD, Stefan OP Hofer, MD PhD.
University Health Network University of Toronto, Toronto, ON, Canada.
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 pre-treatment of human adipose derived stem cells (ASCs) could induce apoptosis in breast cancer cells and therefore confer oncological benefits in reconstruction.
ASCs were isolated from human abdominal fat and expanded in-vitro. ASCs were exposed to interferon-gamma (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 co-cultured with IFN-γ-treated ASCs for 72hours. The effect on MDA-MB-231 cell survival was determined.
Untreated ASCs did not express TRAIL. Exposure to IFN-γ induced TRAIL expression in ASCs in a dose-dependent manner. Co-culture 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
Pre-treatment 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.
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