Establishment of A Piglet Model for Peritoneal Metastasis of Ovarian Cancer

Abstract Background: A piglet model for peritoneal metastasis (PM) of ovarian cancer was developed. It will contribute to the establishment of innovative chemotherapeutical and surgical strategies without any limitation of rodent models.Methods: A total of 12 four- to five-week-old piglets of 7 to 8 kg were used. Two phases of ovarian cancer cell injections were performed with a laparoscopic surgery. In phase I trial, 5.0×106 SK-OV-3 cells in 0.1 ml suspension were inoculated into the omentum, peritoneum, and uterine horns of two piglets twice with a one-week interval. In the phase II trial, 5.0×106 SNU-008 cells in 0.1 ml suspension were injected only into uterine horns with the same time frame because tumor implantation after inoculation of SK-OV-3 cells was not observed at the omentum or peritoneum in the phase I trial. Modified peritoneal cancer index (PCI) score was used to monitor tumorigenesis up to four weeks after inoculation. Tumor tissues disseminated in the peritoneum at four weeks after injection were used for histological examination with hematoxylin and eosin (H&E) and paired-box gene 8 (PAX-8) staining.Results: In the phase I trial, two piglets showed PM with modified PCI scores of 5 and 4 at three weeks after the first inoculation, which increased to 14 and 15 after four weeks, respectively. In the phase II trial, PM was detected in eight of ten piglets, which showed modified PCI scores of 6 to 12 at four weeks after the first inoculation. The overall incidence of PM from the total of 12 piglets after inoculation was 75%. Metastatic tumors were confirmed by immunohistochemical H&E and PAX-8 staining. Conclusions: This study provides strong evidence that piglets can be employed as a model for PM by inoculating ovarian cancer cells form humans. Using two cell lines the PM rate is 75%.