Ex Vivo Culture of Circulating Tumor Cells in the Cerebral Spinal Fluid from Melanoma Patients to Study Melanoma-Associated Leptomeningeal Disease

Leptomeningeal disease from melanoma or MLMD is an aggressive form of metastasis of the meninges, where circulating tumor cells or CTCs, infiltrate into the cerebral spinal fluid. Sadly, there's no effective treatments for MLMD, so understanding its biology will help develop therapies to reduce mortality. Recent reports have shown how CTCs can colonize the nutrient scar CSF environment, such as utilizing the iron scavenging ability to enhance their survival and complement C3 to promote the invasion into the cerebral spinal fluid via the choroid plexus.

Therefore, CTCs are very good tools to study MLMD. The biggest challenge in studying CSF CTCs is the overall lack of preclinical model and the scarcity of these cells. Finding ways to grow these rare and fragile cells from patients and generating a xenograft model will greatly benefit researchers in understanding MLMD pathology and designing rational therapies.

We have developed a method which successfully propagated CSF CTCs from MLMD patients in-vitro and in-vivo, which provided us the ability to perform molecular and functional analyses of MLMD cells, as well as efficacy study in xenograft models. Though the current methodologies is imperfect, but being able to culture and expand CSF CTCs from melanoma patients for the first time, gave us insights on the importance of understanding the CSF Microenvironments.