Introduction

Brain metastases (BMs) derived from ovarian cancer (OC) are rare but lethal, and current treatments are ineffective for this complication. Due to a lack of pre-clinical models and knowledge of the mechanisms involved in developing these BMs, there are no established clinical guidelines for treating patients. Enhancing our comprehension of the molecular mechanisms governing OC cell invasion and survival within the brain environment would uncover potential therapeutic vulnerabilities, paving the way for innovative treatment strategies. Our project aims to create a high-throughput ex vivo model to study OC cell invasion and brain environment alterations.

Methods

We are developing a high-throughput organotypic co-culture model by combining murine brain slices with OC cells. Diverse OC cell line models, reflecting various genomic aberrations, enable investigation of their impact on brain invasion. Cancer cells can be placed juxtaposed to the brain slices in a matrigel sphere or placed directly on the slices as a suspension. This innovative approach allows testing of 50 distinct co-culture conditions within a single mouse brain.

Results

Our co-culture model allows the observation of OC cells invasion from matrigel to the brain slices. Additionally, when cells are directly applied to brain slices, we can observe their attachment and the formation of cell islands. Our first data show that the BRCA1 defect and Myc amplification in OC cells appear to allow better invasion and colonization of brain slices than parental cell lines.

Conclusions

The establishment of this advanced model not only enables high-throughput investigations of BMs but also represents a crucial step toward unravelling the complexities of OC BMs' interaction with the brain environment. By deciphering the underlying mechanisms, we would open avenues for identifying novel therapeutic targets, offering hope for improved outcomes and tailored treatments for patients.