Scientific Publications by FDA Staff

Cancer 2012 Nov 15;118(22):5698-708

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

Jain M, Zhang L, He M, Patterson EE, Nilubol N, Fojo AT, Joshi B, Puri R, Kebebew E

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 (IL13R¿2) in some human malignancies. METHODS.: The authors evaluated IL13R¿2 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 R¿2 knockdown in vitro. The sensitivity of 2 ACC cell lines (NCI-H295R [high IL13R¿2 expression] and SW13 [low IL13R¿2 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.: IL13R¿2 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). IL13R¿2 protein expression increased in cells that were treated with IL-13 ligand along with cell invasion (P < .05). Direct IL13R¿2 knockdown decreased cellular proliferation and invasion (P < .05). CONCLUSIONS.: The current results indicated that IL13R¿2 is overexpressed in ACC and regulates cell invasion and proliferation. IL13R¿2 is a novel therapeutic target for the treatment of human ACC.