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.
Highlights
Ovarian cancer (OvCa) is the most lethal among gynecologic malignancies, taking an estimated 14,000 lives in the United States in 2018 [1]
To assess if human ovarian carcinomas could develop in severe combined immune deficient (SCID) pigs, a total of four SCID (S1, S2, S3, and S4) and two nonSCID (NS1 and NS2) pigs were injected with ovarian serous papillary carcinoma (OSPC)-ARK1 cells
Due to limited female SCID availability, we injected two female and two male SCID pigs in this initial study to answer our question of if OSPC-ARK1 cells were capable of developing tumors ectopically in immunocompromised pigs
Summary
Ovarian cancer (OvCa) is the most lethal among gynecologic malignancies, taking an estimated 14,000 lives in the United States in 2018 [1]. X-ray computer tomography (CT) [3] is the most widely used imaging modality for evaluating peritoneal spread in OvCa for presurgical planning, yet there are well acknowledged “blind-spots” where tumor spread cannot be seen as the contrast between normal tissue and tumors is insufficient to discriminate one tissue type from another. Methods to enhance tumor detection are being developed for a variety of imaging modalities, including magnetic resonance imaging (MRI) and positron emission tomography (PET), making use of various targeting mechanisms to target ovarian cancers. Clinical trials for use of OTL38 are already beginning to recruit patients with folate receptor positive ovarian cancer for the use of this fluorescent molecule during cytoreduction or debulking surgeries [10]
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