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Front Oncol. 2019 Jan 22;9:9. doi: 10.3389/fonc.2019.00009. eCollection 2019.

Human Ovarian Cancer Tumor Formation in Severe Combined Immunodeficient (SCID) Pigs.

Author information

1
Department of Animal Science, Iowa State University, Ames, IA, United States.
2
Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, United States.
3
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, United States.
4
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
5
Department of Radiology, Michigan State University, East Lansing, MI, United States.
6
Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI, United States.
7
Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, United States.

Abstract

Ovarian cancer (OvCa) is the most lethal gynecologic malignancy, with two-thirds of patients having late-stage disease (II-IV) at diagnosis. Improved diagnosis and therapies are needed, yet preclinical animal models for ovarian cancer research have primarily been restricted to rodents, for data on which can fail to translate to the clinic. Thus, there is currently a need for a large animal OvCa model. Therefore, we sought to determine if pigs, being more similar to humans in terms of anatomy and physiology, would be a viable preclinical animal model for OvCa. We injected human OSPC-ARK1 cells, a chemotherapy-resistant primary ovarian serous papillary carcinoma cell line, into the neck muscle and ear tissue of four severe combined immune deficient (SCID) and two non-SCID pigs housed in novel biocontainment facilities to study the ability of human OvCa cells to form tumors in a xenotransplantation model. Tumors developed in ear tissue of three SCID pigs, while two SCID pigs developed tumors in neck tissue; no tumors were detected in non-SCID control pigs. All tumor masses were confirmed microscopically as ovarian carcinomas. The carcinomas in SCID pigs were morphologically similar to the original ovarian carcinoma and had the same immunohistochemical phenotype based on expression of Claudin 3, Claudin 4, Cytokeratin 7, p16, and EMA. Confirmation that OSPC-ARK1 cells form carcinomas in SCID pigs substantiates further development of orthotopic models of OvCa in pigs.

KEYWORDS:

Claudin; ovarian cancer; preclinical animal model; severe combined immunodeficient; swine

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