Abstract
ObjectiveStudy 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.MethodsMesothelin 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.ResultsSignificant 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).ConclusionThe results support the utility of the hen as a novel model for preclinical studies of mesothelin as a biomarker and a target for immunotherapy.
Highlights
Study of the hen immune system led to seminal contributions to basic immunological principles [1]
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
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)
Summary
Study of the hen immune system led to seminal contributions to basic immunological principles [1]. Recent studies of spontaneous ovarian cancer in the laying hen suggest it would be a valuable model for studies of ovarian tumor immunology. Increased mesothelin protein expression was reported in 70% of ovarian epithelial tumors and up to 100% of serous papillary ovarian cancer [21,22,23,24,25,26,27,28]. The frequently elevated expression of mesothelin in cancer cells compared to normal cells and the immune response to mesothelin [32,34,35,36,37] have led to exploration of mesothelin as a therapeutic target for ovarian cancers [26,31,38,39]
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