BSLD-06 UNVEILING THE RE-PROGRAMMING OF CHOROID PLEXUS AND LEPTOMENINGEAL METASTASIS

Abstract Leptomeningeal metastasis (LM) is an increasingly common, fatal complication of breast and lung cancer. Despite aggressive treatment, neurologic deficits accumulate rapidly, patients generally succumb to LM within months. We must expand our limited mechanistic knowledge this disease. Under homeostatic conditions, choroid plexus (ChP), highly vascularized structures the brain ventricles, restrict entry macromolecules cells into leptomeninges; however, select cancer can cross barrier grow leptomeningeal space. hypothesize that interactions between ChP niche alter both cells, ultimately supporting LM. During neurogenesis, display substantial extracellular matrix (ECM) remodeling, which elegantly modulated by dynamic spatiotemporal regulation MMPs, Wnt signaling, among other effector proteins. Similarly, 2-photon imaging collected from mice harboring revealed a profound ECM remodeling when compared with naïve mice. This was accompanied increased levels MMP2 MMP9 in CSF. Furthermore, single-cell-RNA-sequencing reveals top differentially expressed pathway metastatic comparison normal ChP, role for developmental signaling Interestingly, SPARC, major modulator tissue repair essential component stem cell chemoattractant factors secreted subventricular zone (SVZ), enriched mouse suggesting SVZ- ChP-secreted signals are key progression. The use clinically-annotated human samples models LM, integration transcriptomics proteomics enabled us identify pathways, capture re-programming unlock space cells. timeframe evolution will be further analysis at different stages