Ccn1 Induces Death of Esophageal Adenocarcinoma: Trick or Trail?

BackgroundSelectively to kill cancer cells has always been a dream of all oncologists. TRAIL has shown promising effect in several types of cancer. A recent study demonstrated a synergistic apoptotic effect of TRAIL and CCN1 in prostate cancer. This study is to investigate the role of CCN1 in esophageal adenocarcinoma (EAC).MethodsExpression of CCN1 and TRAIL were assessed in EAC cells (OE33) and the tumor tissue by quantitative PCR. Normal esophageal cells (Het‐1A) and tissue were used as control.Results(1) CCN1 expression was down by 65% (P < 0.01, N = 15) in OE33 cells compared in Het‐1A cells; and by 95% (P < 0.05, N = 3 normal and 12 EAC) in EAC tumors compared in normal esophageal tissue. (2) OE33 cells expressed TRAIL receptors but not TRAIL ligand, while Het‐1A cells just the opposite. (3) CCN1 up‐regulated pro‐apoptotic genes (e.g. TRADD 181 fold) in OE33 cells, but promoted anti‐apoptotic genes (e.g. BIRC5 137 fold) in Het‐1A cells. (4) TRAIL induced apoptosis in OE33 cells but not in Het‐1A cells. TRAIL and CCN1 combination increased apoptosis by 35% (P < 0.01, N = 3) in OE33 cells. (5) Mixed culture of OE33 and Het‐1A cells caused massive death of OE33 cells.ConclusionsTRAIL can selectively kill EAC cells without harming normal esophageal cells due to the lack of receptor, and CCN1 can enhance the effect. Expression of TRAIL receptors but not the ligand is a strategy of EAC to escape potential cell death. The study was supported by the VA Merit Review.