Human ovarian cancer tumor formation in severe combined immunodeficient (SCID) pigs Journal Article


Authors: Boettcher, A. N.; Kiupel, M.; Adur, M. K.; Cocco, E.; Santin, A. D.; Bellone, S.; Charley, S. E.; Blanco-Fernandez, B.; Risinger, J. I.; Ross, J. W.; Tuggle, C. K.; Shapiro, E. M.
Article Title: Human ovarian cancer tumor formation in severe combined immunodeficient (SCID) pigs
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. © 2019 Boettcher, Kiupel, Adur, Cocco, Santin, Bellone, Charley, Blanco-Fernandez, Risinger, Ross, Tuggle and Shapiro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: ovarian cancer; swine; claudin; severe combined immunodeficient; preclinical animal model
Journal Title: Frontiers in Oncology
Volume: 9
ISSN: 2234-943X
Publisher: Frontiers Media S.A.  
Date Published: 2019-01-01
Start Page: 9
Language: English
DOI: 10.3389/fonc.2019.00009
PROVIDER: scopus
PMCID: PMC6349777
PUBMED: 30723704
DOI/URL:
Notes: Article -- Export Date: 1 May 2019 -- Source: Scopus
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  1. Emiliano Cocco
    31 Cocco