Interleukin-13 receptor alpha2 chain: a potential biomarker and molecular target for ovarian cancer therapy.
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 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.


METHODS
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.


RESULTS
Immunohistochemical analyses revealed that 83% of ovarian cancer specimens express IL-13Ralpha2, 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-13Ralpha2. 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-13Ralpha2 was detected in the serum of mice with peritoneal metastasis, and the level decreased to baseline in the treated group.


CONCLUSIONS
IL-13Ralpha2 is a promising target for ovarian cancer therapy, and the soluble form of IL-13R may be a possible surrogate marker for disease monitoring.
Kioi
Mitomu
M
Tumor Vaccines and Biotechnology Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Kawakami
Mariko
M
Shimamura
Takeshi
T
Husain
Syed R
SR
Puri
Raj K
RK
D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood / Q000235:genetics; D002100:Cachexia / Q000517:prevention & control; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018793:Interleukin-13 / Q000737:chemistry / Q000494:pharmacology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000097:blood / Q000517:prevention & control / Q000556:secondary; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000235:genetics; D053660:Receptors, Interleukin-13; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D014408:Biomarkers, Tumor; D003603:Cytotoxins; C508181:IL13RA1 protein, human; C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13