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An Essential Role of Maspin in Embryogenesis and Tumor Suppression.

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2017

Cancer Res. 2017 Feb 15;77(4):886-896. doi: 10.1158/0008-5472.CAN-16-2219. Epub 2016 Dec 6.

An Essential Role of Maspin in Embryogenesis and Tumor Suppression.

SH Dzinic;MM Bernardo;X Li;R Fernandez-Valdivia;YS Ho;QS Mi;S Bandyopadhyay;F Lonardo;S Vranic;DS Oliveira;RD Bonfil;G Dyson;K Chen;A Omerovic;X Sheng;X Han;D Wu;X Bi;D Cabaravdic;U Jakupovic;M Wahba;A Pang;D Harajli;WA Sakr;S Sheng

Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan. Tumor Biology and Microenvironment Program, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan. Institute of Environmental Health Sciences, Wayne State University School of Medicine, Detroit, Michigan. Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan. Department of Dermatology, Henry Ford Health Systems, Detroit, Michigan. Division of Experimental Pathology, Department of Pathology, University Clinical Center, Sarajevo, Bosnia and Herzegovina. Department of Urology, Wayne State University School of Medicine, Detroit, Michigan. Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan. Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Detroit, Michigan. Mucosal Immunology Studies Team, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland. Department of Obstetrics and Gynecology, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China. Peking University Health Science Center, The Third Affiliated Hospital, Beijing, P.R. China. Department of Internal Medicine, Sinai Grace Hospital, Detroit Medical Center, Detroit, Michigan.

Service type: Knockout mice

Abstract

Maspin (SerpinB5) is an epithelial-specific tumor suppressor gene product that displays context-dependent cellular functions. Maspin-deficient mouse models created to date have not definitively established maspin functions critical for cancer suppression. In this study, we generated a mouse strain in which exon 4 of the Maspin gene was deleted, confirming its essential role in development but also enabling a breeding scheme to bypass embryonic lethality. Phenotypic characterization of this viable strain established that maspin deficiency was associated with a reduction in maximum body weight and a variety of context-dependent epithelial abnormalities. Specifically, maspin-deficient mice exhibited pulmonary adenocarcinoma, myoepithelial hyperplasia of the mammary gland, hyperplasia of luminal cells of dorsolateral and anterior prostate, and atrophy of luminal cells of ventral prostate and stratum spinosum of epidermis. These cancer phenotypes were accompanied by increased inflammatory stroma. These mice also displayed the autoimmune disorder alopecia aerate. Overall, our findings defined context-specific tumor suppressor roles for maspin in a clinically relevant model to study maspin functions in cancer and other pathologies. Cancer Res; 77(4); 886-96. ©2017 AACR.

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