Lombardi Comprehensive Cancer Center, Laboratory for Immuno-Oncology, Georgetown University Medical Center, Washington, DC, USA.
Institut National de la Santé et de la Recherche Médicale, Inserm U1292, Grenoble, France.
Methods Mol Biol. 2024;2728:77-85. doi: 10.1007/978-1-0716-3495-0_6.
Gestational trophoblastic diseases (GTD) are a group of pregnancy-related disorders representing rare human tumors. Among GTD is the gestational choriocarcinoma (CC), which is a highly malignant gestational trophoblastic tumor that causes high mortality without timely treatment. The incidence of CC is about 1 in 50,000 pregnancies in developed countries and even higher in developing countries. CC developed from molar pregnancies exhibits even higher incidence rates (3-20 in 1000 pregnancies). In the present invention, we developed the first orthotopic animal model of CC. We demonstrate how to mimic the development of this cancer and observe rapid metastasis, which is seen in CC patients, by injecting the luciferase-positive JEG-3 (JEG-3-Luc) cells directly in the placenta of gravid SCID mice. Gravid mice were injected at 7.5 days post coitus (dpc) and followed throughout gestation to assess the parameters of CC development and metastasis. Mice imaged at day 19.5 dpc showed placental tumor development and large sites of metastases in the liver, spleen, lung, and peritoneum. This finding emphasizes the importance of placental vascularization in the rapid dissemination of tumor cells. Morphological analyses and histopathological examinations were performed to confirm JEG-3 cell dissemination in different organs of the gravid mice. This is the first time a CC model was developed by injection of tumor cells within the placenta. This technique offers a new tool to study tumor progression with strong perspectives to test anti-tumor agents in vivo.
妊娠滋养细胞疾病（GTD）是一组与妊娠相关的疾病，代表罕见的人类肿瘤。GTD 中包括绒癌（CC），这是一种高度恶性的妊娠滋养细胞肿瘤，如果不及时治疗，死亡率很高。在发达国家，CC 的发病率约为每 50000 次妊娠中出现 1 例，在发展中国家甚至更高。来源于葡萄胎的 CC 发病率更高（每 1000 次妊娠中有 3-20 例）。在本发明中，我们建立了第一个 CC 的原位动物模型。我们通过直接向怀孕的 SCID 小鼠胎盘内注射荧光素酶阳性的 JEG-3（JEG-3-Luc）细胞，模拟这种癌症的发展，并观察到快速转移，这在 CC 患者中可见。怀孕的小鼠在受精后 7.5 天（dpc）注射，并在整个妊娠期进行监测，以评估 CC 发展和转移的参数。在 19.5 天 dpc 时对小鼠进行成像，显示胎盘肿瘤的发展和肝脏、脾脏、肺和腹膜中的大转移灶。这一发现强调了胎盘血管化在肿瘤细胞快速扩散中的重要性。进行了形态学分析和组织病理学检查，以确认 JEG-3 细胞在怀孕小鼠的不同器官中的扩散。这是首次通过在胎盘内注射肿瘤细胞来建立 CC 模型。该技术为研究肿瘤进展提供了一种新工具，具有在体内测试抗肿瘤药物的广阔前景。
