Inhibition of Human Embryonal Carcinoma Cancer Stem Cells by Co-Culture with Their Differentiated Progeny
Michael F Gallagher, Brendan Ffrench, Claudia Gasch, Aoife Cooke, John J O'Leary. University of Dublin, Trinity College, Dublin, Ireland
Background: Cancer stem cells (CSCs) and the differentiated cells they produce co-exist in tumors. However, our understanding of their interaction is sparse. Addressing this, undifferentiated and differentiated cells were co-cultured and their interaction assessed.
Design: Pluripotent NTera2 human Embryonal Carcinoma (hEC) CSCs were terminally differentiated via retinoic acid. Undifferentiated and differentiated cells were co-cultured at ratios of 1:1 and 1:9. Proteins secreted in conditioned media were identified trough 'Quantikine' array analysis (Ray Biotech).
Results: 1:1 co-culture of undifferentiated and differentiated cells had little effect on the proliferation or viability of either cell type. In contrast, 1:9 co-culture inhibited the proliferation of undifferentiated hEC cells. Inhibition was more pronounced when hEC cells were differentiated for longer (1 week vs. 2 weeks). Conditioned media from differentiated cells was found to be sufficient for partial inhibition. Quantikine array analysis identified several proteins, including receptors, secreted by differentiated cells, which may be responsible for this phenomenon.
Conclusions: Proliferation of undifferentiated CSCs can be inhibited by products secreted by their differentiated progeny. Inhibition requires an excess of differentiated cells and is more pronounced when with longer differentiated cells. Data suggests that proteins secreted by differentiated cells may a useful for therapeutic inhibition of CSC proliferation.
Category: Gynecologic & Obstetrics
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 194, Wednesday Afternoon