Secretion of Specific Toll-Like Receptor Signaling Proteins in the Response of Embryonal Carcinoma Cancer Stem Cells to Differentiation, Hypoxia and Chemotherapy
Michael F Gallagher, Aoife Cooke, John J O'Leary. University of Dublin, Trinity College, Dublin, Ireland
Background: We have previously reported that Toll-Like Receptor 4 (Tlr4) and Myeloid-Differentiation Primary Response Gene 88 (MyD88) are putative indicators of overall outcome in ovarian cancer and involved in differentiation-, hypoxia- and chemo-resistance in human embryonal carcinoma (hEC) cancer stem cells (CSCs). The Tlr4-MyD88 receptor-modulator complex of TLR signaling is known to regulate the profile of pro-inflammatory proteins secreted by the cell. In this study, these secreted proteins were profiled.
Design: Conditioned media from pluripotent NTera2 and nullipotent 2102Ep hEC CSCs grown in differentiation, hypoxia and chemotherapy conditions was assessed for the expression of secreted proteins. Proteins secreted were identified through 'Quantikine' array analysis (Ray Biotech).
Results: Populations of secreted proteins were identified for each treatment. Differential expression of Tlr4-MyD88 correlated to specific populations of secreted proteins. These populations differed, even when similar Tlr4-MyD88 expression patters were observed. This profile was similarly specific for cells in which MyD88 had been knocked down. Of note was the altered expression of receptor proteins
Conclusions: Tlr4-MyD88 signaling plays a role in ovarian tumorigenesis. It has been shown that proteins secreted by cells in various cancer-related conditions are specific to the treatment as well as the expression pattern of Tlr4-MyD88. Overall, the data present a model whereby receptor proteins are secreted by malignant cells to, perhaps, act as biochemical sponges to prevent ligands reaching receptors on the cell surface.
Category: Gynecologic & Obstetrics
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 190, Wednesday Morning