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Development and characterization of a clinically useful animal model of epithelial ovarian cancer in the Fischer 344 rat.

  • Author(s): Rose, GS
  • Tocco, LM
  • Granger, GA
  • DiSaia, PJ
  • Hamilton, TC
  • Santin, AD
  • Hiserodt, JC
  • et al.
Abstract

OBJECTIVE: Our purpose was to develop and characterize a spontaneously arising, nonimmunogenic experimental animal model of epithelial ovarian cancer. STUDY DESIGN: NuTu-19 is a cell line derived from a poorly differentiated adenocarcinoma formed in a female athymic mouse after subcutaneous injection of spontaneously transformed Fischer 344 rat ovarian surface epithelial cells. This cell line was injected intraperitoneally into naive, immunocompetent Fischer 344 rats to determine tumor growth and animal survival. Immunogenicity of this cell line was determined by repetitive vaccination of naive rats with either mitomycin C-treated or irradiated (5000 cGy) NuTu-19 cells, followed by intraperitoneal rechallenge with viable tumor cells. Kaplan-Meier survival analysis was used to analyze survival data. Major histocompatibility complex class I and class II and intercellular adhesion molecule-1 cell surface antigens were determined by fluorescence-activated cell sorting analysis. RESULTS: NuTu-19 cells injected intraperitoneally grew progressively as numerous serosal nodules (peritoneum, omentum, diaphragm, liver, bowel), exhibited local tissue invasion and formed malignant ascites in a manner typical for human ovarian epithelial carcinomas. Animal survival was dosage dependent where as few as 10(4) cells were fatal when introduced intraperitoneally; mean animal survival was noted to be approximately 49 days when 10(5) cells were injected intraperitoneally. Repetitive immunizations of animals with large doses (10(7)) of inactivated NuTu-19 cells did not confer immunity to the animals, which all died on subsequent challenge with viable parental tumor cells. NuTu-19 cells expressed high levels of major histocompatibility complex class I and intercellular adhesion molecule-1 cell surface antigens and very low levels of major histocompatibility complex class II antigens. CONCLUSION: This is the first report of a reliable, spontaneously arising, nonimmunogenic epithelial ovarian cancer animal model. Because this model exists in an immunocompetent animal, it will be useful for studying the biologic and immunologic features of ovarian cancer.

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