Rose G S, Tocco L M, Granger G A, DiSaia P J, Hamilton T C, Santin A D, Hiserodt J C
Division of Gynecologic Oncology, University of California, Irvine, Orange, USA.
Am J Obstet Gynecol. 1996 Sep;175(3 Pt 1):593-9. doi: 10.1053/ob.1996.v175.a73595.
Our purpose was to develop and characterize a spontaneously arising, nonimmunogenic experimental animal model of epithelial ovarian cancer.
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.
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.
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.
我们的目的是建立并描述一种自发产生的、非免疫原性的上皮性卵巢癌实验动物模型。
NuTu-19是一种细胞系，它源自一只雌性无胸腺小鼠在皮下注射自发转化的Fischer 344大鼠卵巢表面上皮细胞后形成的低分化腺癌。将该细胞系腹腔内注射到未接触过抗原、具有免疫活性的Fischer 344大鼠体内，以确定肿瘤生长情况和动物存活率。通过用丝裂霉素C处理或照射（5000 cGy）的NuTu-19细胞对未接触过抗原的大鼠进行重复免疫接种，然后腹腔内再次接种活的肿瘤细胞，来确定该细胞系的免疫原性。采用Kaplan-Meier生存分析来分析生存数据。通过荧光激活细胞分选分析来确定主要组织相容性复合体I类和II类以及细胞间黏附分子-1细胞表面抗原。
腹腔内注射的NuTu-19细胞逐渐生长为大量浆膜结节（腹膜、网膜、膈肌、肝脏、肠道），表现出局部组织侵袭，并以人类卵巢上皮癌典型的方式形成恶性腹水。动物存活率呈剂量依赖性，腹腔内注射低至10⁴个细胞就会致命；腹腔内注射10⁵个细胞时，动物平均存活时间约为49天。用大剂量（10⁷）灭活的NuTu-19细胞对动物进行重复免疫接种并不能使动物获得免疫力，所有动物在随后接种活的亲代肿瘤细胞时均死亡。NuTu-19细胞表达高水平的主要组织相容性复合体I类和细胞间黏附分子-1细胞表面抗原，以及极低水平的主要组织相容性复合体II类抗原。
这是关于一种可靠的、自发产生的、非免疫原性的上皮性卵巢癌动物模型的首次报道。由于该模型存在于具有免疫活性的动物体内，它将有助于研究卵巢癌的生物学和免疫学特征。
