Matrix metalloproteinase-9 (MMP-9) degrades the extracellular matrix, contributes
to tumour cell invasion and metastasis, and its elevated level in brain tumour tissues
indicates poor prognosis. High-risk tissue biopsy can be replaced by liquid biopsy;
however, the blood–brain barrier (BBB) prevents tumour-associated components from
entering the peripheral blood, making the development of blood-based biomarkers challenging.
Therefore, we examined the MMP-9 content of small extracellular vesicles (sEVs)—which
can cross the BBB and are stable in body fluids—to characterise tumours with different
invasion capacity. From four patient groups (glioblastoma multiforme, brain metastases
of lung cancer, meningioma, and lumbar disc herniation as controls), 222 serum-derived
sEV samples were evaluated. After isolating and characterising sEVs, their MMP-9 content
was measured by ELISA and assessed statistically (correlation, paired t-test, Welch’s
test, ANOVA, ROC). We found that the MMP-9 content of sEVs is independent of gender
and age, but is affected by surgical intervention, treatment, and recurrence. We found
a relation between low MMP-9 level in sEVs (<28 ppm) and improved survival (8-month
advantage) of glioblastoma patients, and MMP-9 levels showed a positive correlation
with aggressiveness. These findings suggest that vesicular MMP-9 level might be a
useful prognostic marker for brain tumours.
