Abstract B29: Effects of prenatal exposure to cancer treatment: The development of a placental murine xenograft model

The aim of this study was to develop a suitable murine xenograft model to examine the possible effect of drugs or chemotherapeutic agents on the placental tissue.

Methods: The test population consisted of 4 examination groups of six immunodefficient nude mice. After the mice were ovariectomised and hormonal stimulated (17b estradiol and progesterone pellets), placental tissue derived from first and third trimester pregnancies was engrafted subcutaneously bilateral in the interscapular fat pad. hCG (human chorionic gonadotrophin) secretion was measured in serum and urine by an enzyme-linked immunosorbent assay (ELISA). To examine the viability and preservation of the placental tissue, factors for proliferation (hCG, Ki67), apoptosis (cleaved caspase-3) and murine angiogenesis (CD31) were evaluated by immunohistochemistry (IHC). The expression level of genes relevant for the angiogenesis (IGF-1, PGF, IGF-2), inflammation (eNOS) and proliferation (Flk-1, Flt-1) was compared by using reverse transcription- quantitative real-time polymerase chain reaction (RT-qPCR).

Results: Comparing the placental tissue before and after engraftment, we found preserved structure and histological features. Also, the PCR analysis showed preserved genetic characteristics of the primary engrafted placental tissue. hCG secretion, evaluated by ELISA in the urine and blood, was present for 3 weeks.

Conclusion: We created a murine xenograft model with proven stability and preserved structure of the engrafted placental tissue for 3 weeks. This established murine xenograft model will be useful to examine the effect of cancer treatment; moreover, it could serve as a model for other fetal toxicity studies.

Citation Format: Magali Verheecke, Wout Devlies, Els Hermans, Frédéric Amant. Effects of prenatal exposure to cancer treatment: The development of a placental murine xenograft model. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr B29.