DEVELOPMENT AND CHARACTERIZATION OF A CLINICALLY USEFUL ANIMAL-MODEL OF EPITHELIAL OVARIAN-CANCER IN THE FISCHER-344 RAT

OBJECTIVE: Our purpose was to develop and characterize a spontaneously arising, nonimmunogenic experimental animal model of epithelial ovari an cancer. STUDY DESIGN: NuTu-19 is a cell line derived from a poorly differentiated adenocarcinoma formed in a female athymic mouse after s ubcutaneous injection of spontaneously transformed Fischer 344 rat ova rian surface epithelial cells. This cell line was injected intraperito neally into naive, immunocompetent Fischer 344 rats to determine tumor growth and animal survival. Immunogenicity of this cell line was dete rmined by repetitive vaccination of naive rats with either mitomycin C -treated or irradiated (5000 cGy) NuTu-19 cells, followed by intraperi toneal rechallenge with viable tumor cells. Kaplan-Meier survival anal ysis was used to analyze survival data. Major histocompatibility compl ex class I and class II and intercellular adhesion molecule-1 cell sur face antigens were determined by fluorescence-activated cell sorting a nalysis. RESULTS: NuTu-19 cells injected intraperitoneally grew progre ssively as numerous serosal nodules (peritoneum, omentum, diaphragm, l iver, bower), exhibited local tissue invasion and formed malignant asc ites in a manner typical for human ovarian epithelial carcinomas. Anim al survival was dosage dependent where as few as 10(4) cells were fata l when introduced intraperitoneally; mean animal survival was noted to be approximately 49 days when 10(6) cells were injected intraperltone ally. Repetitive immunizations of animals with large doses (10(7)) of inactivated NuTu-19 cells did not confer immunity to the animals, whic h all died on subsequent challenge with viable parental tumor cells. N uTu-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 histocampatibility complex class ii antig ens. CONCLUSION: This is the first report of a reliable, spontaneously arising, nonimmunogenic epithelial ovarian cancer animal model. Becau se this model exists in an immunocompetent animal, it will be useful f or studying the biologic and immunologic features of ovarian cancer.