Leptomeningeal metastatic cancer cells induce a permissive choroid plexus vasculature through extracellular-vesicle-derived 5-HIAA signaling - PubMed
21 hours ago
- #5-HIAA Signaling
- #Leptomeningeal Metastasis
- #Choroid Plexus
- Leptomeningeal metastasis (LM) involves cancer cells colonizing the meninges, with the choroid plexus serving as a key barrier.
- The study finds that cancer cells remodel the metabolic microenvironment to create a supportive premetastasis niche in the choroid plexus.
- Extracellular vesicles containing 5-hydroxyindoleacetic acid (5-HIAA) target choroid plexus vessels before initial cancer cell invasion.
- 5-HIAA causes vascular distortion, abnormal hemodynamics, increased permeability, and facilitates cancer cell traversal through the vasculature.
- Mechanistically, 5-HIAA activates the aryl hydrocarbon receptor pathway, leading to aberrant expression of mechanoreceptors and tight junction proteins.
- Elevated 5-HIAA levels in cerebrospinal fluid and choroid plexus indicate a predisposition for metastatic colonization.
- These findings highlight 5-HIAA's role in niche formation and suggest metabolic targets to prevent LM initiation by modulating choroidal plasticity.