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Interleukin-13 receptor α2 chain
A potential biomarker and molecular target for ovarian cancer therapy†
Article first published online: 10 AUG 2006
Published 2006 American Cancer Society
Volume 107, Issue 6, pages 1407–1418, 15 September 2006
How to Cite
Kioi, M., Kawakami, M., Shimamura, T., Husain, S. R. and Puri, R. K. (2006), Interleukin-13 receptor α2 chain. Cancer, 107: 1407–1418. doi: 10.1002/cncr.22134
This article is a US Government work and, as such, is in the public domain in the United States of America.
- Issue published online: 1 SEP 2006
- Article first published online: 10 AUG 2006
- Manuscript Accepted: 26 MAY 2006
- Manuscript Revised: 22 MAY 2006
- Manuscript Received: 21 FEB 2006
- ovarian cancer;
- targeted therapy
Epithelial ovarian cancer demonstrates high mortality due to diagnosis at an advanced stage. In the search for a biomarker for early diagnosis and a target for therapy, the issue of whether interleukin-13 receptor (IL-13R), shown to be expressed on a variety of human cancers, is expressed in ovarian tumor samples was explored. In addition, whether this receptor serves as a biomarker and can be targeted by IL-13 cytotoxin was examined.
IL-13R expression in 15 normal and 68 ovarian tumor tissue samples was determined by immunohistochemistry. Correlation between clinicopathologic features and IL-13R expression was analyzed. The efficacy of IL-13R-directed cytotoxin was determined in mice with subcutaneous, orthotopic, and peritoneal metastatic ovarian cancer.
Immunohistochemical analyses revealed that 83% of ovarian cancer specimens express IL-13Rα2, a high-affinity IL-13R subunit chain, whereas normal ovary samples expressed none or very low levels. The majority of clear cell ovarian carcinomas with the worst prognosis showed strong staining for IL-13Rα2. IL-13 cytotoxin was highly cytotoxic to the IGROV-1 ovarian cancer cell line in vitro, and it mediated significant antitumor activity against a xenografted tumor model. The antitumor effects were confirmed by treating orthotopically implanted or peritoneal metastatic ovarian tumors, which showed significant extension of survival in immunodeficient mice. IL-13 cytotoxin also prevented cachexia in treated mice. The soluble form of IL-13Rα2 was detected in the serum of mice with peritoneal metastasis, and the level decreased to baseline in the treated group.
IL-13Rα2 is a promising target for ovarian cancer therapy, and the soluble form of IL-13R may be a possible surrogate marker for disease monitoring. Cancer. Published 2006 by the American Cancer Society.