Extracellular vesicles carrying ECM regulators as biomarkers and mediators in brain metastases

• Applicant: Amanda Salviano da Silva Literski, Ph.D.
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 579753501

Brain metastases (BrM) remain major clinical challenges due to their poor prognosis and limited detection methods. Current diagnostic approaches are invasive and often identify tumors at advanced stages. Extracellular vesicles (EVs) are released in elevated amounts from tumor cells, carrying molecular cargo reflective of their origin to liquid biopsies. Thus, EVs offer a minimally invasive alternative for early detection and monitoring of these tumors. EVs are also mediators of tumor progression and invasion. These functional roles involve the transport of relevant molecules, such as regulators of the extracellular matrix (ECMreg), which are often overexpressed in multiple cancers. It seems logical that their association with EVs enhances their functional activities and further spread them to distant niches. Nevertheless, comparative and functional analyses of ECMreg-EV profiles in BrM remain underexplored. The applicant has investigated circulating EVs and their cargo in glioblastoma, where some ECMreg proteins have been highlighted. The major hypothesis is that circulating EVs from BrM patients also exhibit distinct surface levels of these ECMreg markers, and these ECMreg+ EVs may play a number of pro-metastatic roles. Within three proposed work packages, the applicant herein aims to: 1) investigate EVs transporting ECMreg proteins in patients with BrM (originating from NSCLC, melanoma, or breast cancer), by characterizing their circulating levels in plasma and biomarker utilities for disease detection, monitoring and tumor subtyping; 2) Establish a method to purify from plasma the EV populations identified as clinically relevant in WP1, and characterize their molecular cargo; and 3) perform functional studies to identify the impact of these selected EV population in contact with primary glioma cells and their ability to cross a blood-brain-barrier (BBB) model in vitro. The data generated by this study has a strong potential to improve the diagnostic and prognostic landscape for patients with brain metastases, and help the neurosurgery community to understand if and how EVs influence viability and intercellular communication between distant tumor niches, thus increasing the comprehension of metastatic mechanisms to the brain.

• DFG Programme: Research Grants