Resumen
Medulloblastoma is the most prevalent malignant paediatric brain tumour, where metastasis and recurrence account for 95% of medulloblastoma-associated deaths. Secretion of extracellular vesicles (EVs) has emerged as a pivotal mediator for communication in the tumour microenvironment during metastasis. We investigated whether sEVs and exosomes mediate communication between medulloblastoma cells and their surroundings to drive metastasis. Metastatic exosomes were shown to potentiate medulloblastoma migration via the active protease, matrix metalloproteinase-2 (MMP-2), on their surface, resulting in degradation of the extracellular matrix (ECM) and creating routes for medulloblastoma cells to invade into the surrounding environment. Knockdown of MMP-2 and its activator extracellular matrix metalloproteinase inducer (EMMPRIN) reduced this invasive potential. Our observations also highlight the potential of MMP-2 as a biomarker for metastatic medulloblastoma. Together, our findings reveal unique insights into the pathogenesis of medulloblastoma and highlight the need to explore alternative therapeutic approaches to impair MMP-driven mechanisms of tumour invasion and migration.