Evaluation of matrix metalloproteinase type IV-collagenases in serum of patients with tumors of the central nervous system

Abstract

The basement membrane collagen IV-degrading matrix metalloproteinases -2 and -9 (MMPs) are most often linked to the malignant phenotype of tumor cells by playing a critical role in invasion, metastasis, angiogenesis, and vasculogenesis. We verified the activity of these two MMPs in the sera of patients affected by brain tumors (20 gliomas, 28 meningiomas and 20 metastasis) by zymography. The sera of 25 healthy volunteers with no concomitant illnesses were used for controls. Zymography showed four dominant gelatinolytic bands of 240, 130, 92 (MMP-9) and 72 (MMP-2) kDa. No statistically significant variations of MMP-2 proteolytic activity between patients and healthy individuals were observed. On the contrary, MMP-9 (both monomeric and multimeric forms) lytic activities were significantly higher in tumors specimens compared to healthy controls (p < 0.001). Moreover, MMP-9 immunohistochemistry revealed: (1) a strong reactivity in neoplastic vessels of high-grade gliomas showing an inverse correlation with serum multimeric gelatinolytic activity; (2) a cytoplasmatic reactivity in meningiomas with a significantly increase in atypical meningioma compared with low-grade ones (p = 0.036); (3) a positive correlation between MMP-9 and Ki-67 (Sperman Rho coefficient r = 0.418 and p = 0.034). Our results suggest that serum and tissue MMP-9 might provide clinicians additional objective information in intracranial neoplasms. Finally, it should be possible to use MMP-9 as a target for new forms of therapy. Nevertheless, due to the small number of patients included in the study, the conclusion may not be transferable to the general population and therefore further evaluations are needed.

Immunohistochemical analysis of matrix metalloproteinase‑9 predicts papillary thyroid carcinoma prognosis

“…In addition, MMP-9 is an essential mediator of epithelial-mesenchymal transition, which is a key step in tumor progression and metastasis (43). The association between MMP-9 overexpression and the invasiveness of cancer has been reported in numerous studies (32,44–47). In patients with PTC, positive MMP-9 staining is correlated with lymphatic spreading and the degree of tumor infiltration (3).…”

“…MMPs have essential roles in various biological functions, including cell proliferation, differentiation, ECM degradation and remodeling, angiogenesis and cell migration. Furthermore, the expression and activity of MMP-9 are elevated in numerous types of human cancer (32–34). In addition, the IHC positive staining of MMP-9 has been reported in 57.0–92.4% of patients with PTC (3,24).…”

Metalloproteinases and their roles in human cancer

“…Analysis of MMP levels in the sera of patients with primary and metastatic brain tumors demonstrated a significant increase in serum MMP‐9 levels when compared to healthy individuals. No significant difference was found for serum MMP‐2 levels (Ricci et al, ). mRNA expression of MMP‐9 was also identified as a prognostic biomarker that correlated with disease progression and survival in glioblastoma patients (Li et al, ).…”

Glioblastoma: Is There Any Blood Biomarker with True Clinical Relevance?

“…from the same group, and some years later, did not find any correlation with serum MMP-9 levels and tumor size, survival or chemotherapy response, concluding that serum MMP-9 showed no utility in determining glioma disease status in a cohort of 111 GBM patients, and was not a clinically relevant prognostic marker of survival [54]. Ricci S et al tested a series of 60 brain tumors (20 gliomas, 20 meningiomas and 20 metastases) and 25 controls and showed that MMP-9 is significantly increased in the sera from patients with CNS tumors compared to healthy controls [55]. Again, this study had a very small number of patients of each tumor type to allow solid conclusions.…”