BACKGROUND
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 interleukinâ13 receptor (ILâ13R), 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 ILâ13 cytotoxin was examined.
METHODS
ILâ13R expression in 15 normal and 68 ovarian tumor tissue samples was determined by immunohistochemistry. Correlation between clinicopathologic features and ILâ13R expression was analyzed. The efficacy of ILâ13Râdirected cytotoxin was determined in mice with subcutaneous, orthotopic, and peritoneal metastatic ovarian cancer.
RESULTS
Immunohistochemical analyses revealed that 83% of ovarian cancer specimens express ILâ13Rα2, a highâaffinity ILâ13R 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 ILâ13Rα2. ILâ13 cytotoxin was highly cytotoxic to the IGROVâ1 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. ILâ13 cytotoxin also prevented cachexia in treated mice. The soluble form of ILâ13Rα2 was detected in the serum of mice with peritoneal metastasis, and the level decreased to baseline in the treated group.
CONCLUSIONS
ILâ13Rα2 is a promising target for ovarian cancer therapy, and the soluble form of ILâ13R may be a possible surrogate marker for disease monitoring. Cancer. Published 2006 by the American Cancer Society.