The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Ovarian Res. 2010 Mar 31;3:9. doi: 10.1186/1757-2215-3-9.
Ovarian carcinoma is the fourth most common cause of death from cancer in women. Limited progress has been made toward improving the survival rate of patients with this disease in part because of the lack of a good animal model. We present here a model of spontaneous ovarian carcinoma arising in a normal Lewis rat.
A spontaneously occurring tumor of the left ovary was found in a normal Lewis rat during necropsy, which was sectioned for histological examination and placed into single cell suspension. Tumor cells were passaged in vivo by intraperitoneal injection into immunocompetent Lewis rats, and in vitro culture resulted in generation of a cell line. Tumor cells were examined by flow cytometry for expression of estrogen receptor alpha, progesterone receptor, androgen receptor, her-2/neu, epithelial cell adhesion molecule, and CA125. beta-catenin expression and cellular localization was assessed by immunocytochemistry. RNA was harvested for gene expression profiling and studying the expression of cytokines.
The tumor, designated FNAR, could be serially transplanted into Lewis rats and propagated as a cell line in vitro, maintaining the properties of the original tumor. The FNAR cells displayed striking morphologic similarities to human ovarian carcinoma, resembling the endometrioid carcinoma subtype of surface epithelial neoplasms. The cells expressed estrogen receptor alpha, progesterone receptor, androgen receptor, her-2/neu, epithelial cell adhesion molecule, CA125, and nuclear beta-catenin. A gene expression profile showed upregulation of a number of genes that are also upregulated in human ovarian carcinoma.
This reliable model of ovarian carcinoma should be helpful in better understanding the biology of the disease as well as the development of novel treatment strategies.
卵巢癌是女性癌症死亡的第四大常见原因。由于缺乏良好的动物模型，在提高这种疾病患者的生存率方面进展有限。我们在此介绍一种在正常 Lewis 大鼠中自发发生的卵巢癌模型。
在尸体剖检中发现一只正常 Lewis 大鼠的左侧卵巢有一个自发发生的肿瘤，将其切成切片进行组织学检查，并置于单细胞悬液中。肿瘤细胞通过腹腔内注射到免疫功能正常的 Lewis 大鼠体内进行体内传代，体外培养产生了一个细胞系。通过流式细胞术检测肿瘤细胞中雌激素受体α、孕激素受体、雄激素受体、her-2/neu、上皮细胞黏附分子和 CA125 的表达。通过免疫细胞化学评估β-连环蛋白的表达和细胞定位。提取 RNA 进行基因表达谱分析和研究细胞因子的表达。
该肿瘤命名为 FNAR，可连续移植到 Lewis 大鼠体内，并在体外作为细胞系繁殖，保持原始肿瘤的特性。FNAR 细胞表现出与人类卵巢癌非常相似的显著形态学相似性，类似于表面上皮肿瘤的子宫内膜样癌亚型。这些细胞表达雌激素受体α、孕激素受体、雄激素受体、her-2/neu、上皮细胞黏附分子、CA125 和核β-连环蛋白。基因表达谱显示许多基因的上调，这些基因在人类卵巢癌中也上调。
这种可靠的卵巢癌模型应该有助于更好地了解疾病的生物学特性，以及开发新的治疗策略。
