Overexpression of interleukin-13 receptor-α2 in neuroendocrine malignant pheochromocytoma: A novel target for receptor directed anti-cancer therapy

Edwin W. Lai, Bharat H. Joshi, Lucia Martiniova, Ritika Dogra, Toshio Fujisawa, Pamela Leland, Ronald R. De Krijger, Irina A. Lubensky, Abdel G. Elkahloun, John C. Morris, Raj K. Puri, Karel Pacak

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

18 Citaten (Scopus)


Context: Pheochromocytomas and paragangliomas are rare catecholamine- secreting neuroendocrine tumors arising from the adrenal medulla and sympathetic tissues. When complete surgical resection is not an option, the treatment of pheochromocytoma is limited. Objective: The objective of the study was to identify and characterize overexpression of IL-13 receptor-α2 (IL-13Rα2) gene expression in human and murine tumors and verify xenograft mouse pheochromocytoma cell (MPC)-derived tumor's response to a selective cytotoxin. Design/Setting/Patients: Expression of IL13Rα2 was evaluated in a panel of 25 human pheochromocytoma clinical samples by RT-PCR and eight MPC tumors by indirect immunofluorescence assay and RT-PCR. Intervention: The function of IL-13Rα2 in these tumor cells was examined by evaluating tumor sensitivity to a recombinant IL-13-Pseudomonas exotoxin (IL-13PE). Subcutaneous small and large MPC tumors in athymic nude mice (n = 10) were treated intratumorally with IL-13PE (100 μg/kg). Main Outcome Measures: IC 50 and tumor size were measured. Results: IL-13PE immunotoxin was highly cytotoxic to IL-13Rα2-overexpressing MPC cells (IC50 <2.5 ng/ml) in vitro. Furthermore, IL-13PE was highly cytotoxic to sc tumors. Our results showed a statistically significant decrease in tumor size as early as 3 d after initial treatment and further suppressed growth of MPC tumors. All tumors displayed a histological evidence of necrosis in response to IL-13 immunotoxin without any adverse effects in host at this dose. Conclusions: Human and murine neuroendocrine pheochromocytoma overexpress the IL-13Rα2 chain, and an IL-13PE-based receptor-directed anticancer approach may prove useful in treatment for metastatic pheochromocytoma patients.

Originele taal-2Engels
Pagina's (van-tot)2952-2957
Aantal pagina's6
TijdschriftJournal of Clinical Endocrinology and Metabolism
Nummer van het tijdschrift8
StatusGepubliceerd - aug. 2009
Extern gepubliceerdJa


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