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Open Access Research

The hen model of human ovarian cancer develops anti-mesothelin autoantibodies in response to mesothelin expressing tumors

Yi Yu1, Seby L Edassery1, Animesh Barua123, Jacques S Abramowicz2, Janice M Bahr4, Ingegerd Hellstrom5 and Judith L Luborsky12*

Author Affiliations

1 Department of Pharmacology, Rush University Medical Center, 1735 W Harrison Street, Chicago, IL 60612, USA

2 Department of Obstetrics and Gynecology, Rush University Medical Center, 1725 W Harrison Street, Chicago, IL 60612, USA

3 Department of Pathology, Rush University Medical Center, 1750 W Harrison Street, Chicago, IL 60612, USA

4 Department of Animal Sciences, University of Illinois, Urbana-Champagne, 1207 W. Gregory Drive, Urbana, IL 61801, USA

5 Department of Pathology, University of Washington, 300 9th Ave Haborview R&T Rm 710, Seattle, WA 98104, USA

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Journal of Ovarian Research 2011, 4:12  doi:10.1186/1757-2215-4-12

Published: 29 July 2011

Abstract

Objective

Study of the hen immune system led to seminal contributions to basic immunological principles. Recent studies of spontaneous ovarian cancer in the laying hen show strikingly similar tumor types and antigen expression compared to human ovarian cancer, suggesting hens would be valuable for studies of tumor immunology and pre-clinical vaccine development. Circulating mesothelin is a relatively specific marker for human ovarian cancer and autoantibodies to mesothelin were reported. We hypothesized that hen tumors express mesothelin and that circulating anti-mesothelin antibodies occur in response to tumors.

Methods

Mesothelin mRNA expression was analyzed by RT-PCR in hen ovarian tumors and normal ovaries. Mesothelin protein expression was evaluated by immunohistochemistry (IHC) and two-dimensional SDS-PAGE Western blots. Anti-mesothelin antibodies were assessed by immunoassay of sera from hens with normal ovaries and with ovarian tumors.

Results

Significant mesothelin mRNA expression was observed in 57% (12/21) of hen ovarian tumors but not in normal ovaries and was found predominantly in serous tumors as in humans. Mesothelin protein was detected in tumors with mesothelin mRNA by IHC and 2D Western blots, but not in normal ovaries or tumors without mesothelin mRNA. Circulating anti-mesothelin antibodies occurred in 44% (n = 4/9) of hens with ovarian tumors which express mesothelin mRNA and were not found in hens with tumors that did not express mesothelin (n = 0/5) or normal ovaries (n = 0/5).

Conclusion

The results support the utility of the hen as a novel model for preclinical studies of mesothelin as a biomarker and a target for immunotherapy.

Keywords:
Mesothelin; Mesothelin antibodies; Ovarian Cancer; Hens; Animal Model