Murine mesothelin: characterization, expression, and inhibition of tumor growth in a murine model of pancreatic cancer

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Emmanuel,Agle,Steven,Freistaedter,Andrew,Jones,Gwe Zervos (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Background: Mesothelin has attracted much interest as a tumor specific antigen; it has been reported to promotetumor development and to be a good target for cancer treatment. Most studies to date have used humanmesothelin in immunocompromised mice. Since these models do not allow for study of the natural immuneresponse to mesothelin expressing tumors, we have undertaken the characterization of mouse mesothelin so theeffects of this protein can be assessed in immunocompetent mouse strains.Methods: We analyzed mouse mesothelin expression, tissue distribution, shedding and biochemistry. In addition we constructed stable mesothelin overexpressing lines of the pancreatic cancer line Panc02 by two methods and tested them for growth and tumorigencity in vitro and in vivo.Results: We show here that mouse mesothelin is similar to human mesothelin in biochemical characteristics, tumor expression and tissue distribution, suggesting the mouse may be a suitable model for study of mesothelin. Stable overexpression of mesothelin in a pancreatic cancer cell line did not increase cell proliferation or anchorageindependent growth in vitro, suggesting that mesothelin is not necessarily a tumor progression factor. Surprisingly overexpression of mesothelin inhibited tumor formation in vivo in immunocompetent mice.Conclusion: The mouse may be a good model for studying mesothelin in the context of an intact immune response. Mesothelin is not necessarily a tumor progression factor, and indeed mesothelin overexpression inhibited tumor growth in immunocompetent mice.

Additional Information

Publication

Other

Language: English

Date: 2016

Keywords

Mesothelin, Pancreas, Tumor, Proliferation, Immune

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