557. POTENTIAL THERAPEUTIC TARGETS OF TRPV2 AND SLC12A2 IN ESOPHAGEAL ADENOCARCINOMA CANCER STEM CELLS

Abstract Background Cancer stem cells (CSCs) are resistant to current anticancer drugs and radiation. The membrane transporters have recently been reported to play crucial roles for Esophageal adenocarcinoma (EA) CSCs. The aim of our study was to investigate ion channel expression profiles in esophageal adenocarcinoma CSCs (EACSCs) and to examine these potential as therapeutic targets. Methods Using the EA cell line OE33, cells with strong ALDH1A1 activity, a CSC marker, were isolated by flow cytometry. The characteristics of CSCs for the separated cells were verified by sphere formation assay, the expression of CSC markers on real-time reverse transcription-polymerase chain reaction and western blotting, and anti-cancer agent sensitivity assay. Gene expression profiles in EACSCs were examined by a microarray analysis. The transporters, high expression in CSC, were examined the anti-tumor effect of these inhibitors. Results Separated cells formed spheres in low-adhesion plates. The expressions of CSC markers were higher in CSCs than in non-CSCs. The CSCs also exhibited resistance to cisplatin and redifferentiation potential. The microarray analysis showed that the expression of transient receptor potential vanilloid 2 (TRPV2) and solute carrier family 12 member 2 (SLC12A2), which related to ion channels, were upregulated in CSCs. The cytotoxicities of tranilast and furosemide, which were TRPV2 and SLC12A2 inhibitors respectively, were added to cisplatin. Conclusions We revealed that TRPV2 and SLC12A2 are highly expressed in EACSCs and have potential as therapeutic targets for EA.