Interleukin‐13 receptor alpha2 is a novel therapeutic target for human adrenocortical carcinoma

BACKGROUND. Adrenocortical carcinoma (ACC) is a relatively rare but aggressive malignancy with limited therapeutic options. Previous genome‐wide expression studies have demonstrated the overexpression of interleukin‐13 receptor alpha2 (IL13Rα2) in some human malignancies. METHODS. The authors evaluated IL13Rα2 mRNA and protein expression in 21 normal samples, 78 benign samples, 10 primary malignant samples, and 25 metastatic/recurrent samples and performed functional analyses with IL13 ligand and IL13 Rα2 knockdown in vitro. The sensitivity of 2 ACC cell lines (NCI‐H295R [high IL13Rα2 expression] and SW13 [low IL13Rα2 expression]) to a highly specific IL‐13 conjugated with Pseudomonas exotoxin (IL‐13‐PE) also was evaluated in both in vitro and in vivo models. RESULTS. IL13Rα2 was overexpressed in malignant tumors compared with benign and normal samples (15‐fold higher; P < .05). Immunohistochemistry also confirmed higher protein expression in malignant and benign tumors than in normal adrenocortical tissues (P < .05). The half‐maximal inhibitory concentration for IL‐13‐PE was 1.3 ng/mL in the NCI‐H295R cell line and 1000 ng/mL in the SW13 cell line. Mice that received intratumoral or intraperitoneal IL‐13‐PE injection had a significant reduction in tumor size and increased tumor necrosis compared with control groups (P < .05) and also had prolonged survival (P < .05). IL13Rα2 protein expression increased in cells that were treated with IL‐13 ligand along with cell invasion (P < .05). Direct IL13Rα2 knockdown decreased cellular proliferation and invasion (P < .05). CONCLUSIONS. The current results indicated that IL13Rα2 is overexpressed in ACC and regulates cell invasion and proliferation. IL13Rα2 is a novel therapeutic target for the treatment of human ACC. Cancer 2012. © 2012 American Cancer Society. In this study of interleukin‐13 receptor alpha2 (IL13Rα2) expression in 134 human adrenocortical tissue samples, IL13Rα2 is overexpressed in 100% of adrenocortical carcinomas. IL13Rα2 also directly regulates cell invasion and proliferation in adrenocortical carcinoma cells and is identified as a novel therapeutic target for human adrenocortical carcinoma using IL‐13 Pseudomonas exotoxin, in both in vitro and in vivo models.