title: Interleukin-13 receptor alpha2 is a novel therapeutic target for human adrenocortical carcinoma.
abstract: 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.
authors.affiliation: Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Meenu
authors.initials: M
authors.lastname: Jain
authors.forename: Lisa
authors.initials: L
authors.lastname: Zhang
authors.forename: Mei
authors.initials: M
authors.lastname: He
authors.forename: Erin E
authors.initials: EE
authors.lastname: Patterson
authors.forename: Naris
authors.initials: N
authors.lastname: Nilubol
authors.forename: Antonio T
authors.initials: AT
authors.lastname: Fojo
authors.forename: Bharat
authors.initials: B
authors.lastname: Joshi
authors.forename: Raj
authors.initials: R
authors.lastname: Puri
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018268:Adrenocortical Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005098:Exotoxins / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018793:Interleukin-13 / Q000627:therapeutic use*; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D005098:Exotoxins; C521502:IL13-PE38; D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins