In Vivo Quantitative Assessment of Gestational Choriocarcinoma Development and Progression Using Luminescent Trophoblast Cells.

Abstract

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 7.5days post coitus (dpc) and followed throughout gestation to assess the parameters of CC development and metastasis. Mice imaged at day 19.5dpc 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.