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Published on: January 14, 2011
Interleukin-13 receptor alpha2 is a novel therapeutic target for human adrenocortical carcinoma
Meenu Jain1, Lisa Zhang, Mei He
1Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
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.
Insights
Interleukin-13 receptor alpha2 (IL13Rα2) is overexpressed in adrenocortical carcinoma (ACC), driving tumor cell invasion and proliferation. Targeting IL13Rα2 presents a promising new therapeutic strategy for ACC patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Adrenocortical carcinoma (ACC) is an aggressive cancer with limited treatment options.
- Interleukin-13 receptor alpha2 (IL13Rα2) has been observed to be overexpressed in several human cancers.
Purpose of the Study:
- To investigate the role of IL13Rα2 in adrenocortical carcinoma (ACC).
- To evaluate IL13Rα2 as a potential therapeutic target for ACC.
Main Methods:
- Quantified IL13Rα2 mRNA and protein expression in normal, benign, and malignant ACC tissues.
- Performed in vitro functional analyses using IL13 ligand and IL13Rα2 knockdown.
- Assessed the efficacy of IL-13 conjugated with Pseudomonas exotoxin (IL-13-PE) in ACC cell lines and in vivo models.
Main Results:
- IL13Rα2 was significantly overexpressed (15-fold) in malignant ACC tumors compared to normal and benign samples.
- IL-13-PE demonstrated potent cytotoxicity against high IL13Rα2-expressing ACC cells (NCI-H295R) in vitro and reduced tumor growth in vivo.
- IL13Rα2 expression correlated with increased cell invasion, while its knockdown reduced proliferation and invasion.
Conclusions:
- IL13Rα2 is a key regulator of cell invasion and proliferation in adrenocortical carcinoma.
- IL13Rα2 represents a novel and promising therapeutic target for human ACC.
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