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

Serena Ricci,Dario Bruzzese,Angelina Di Carlo,Carmela Peca,Francesco G Sgulò,Marialaura Del Basso De Caro,Elia Guadagno,Francesco Maiuri

doi:10.1007/s11060-016-2297-4

Serena Ricci, Dario Bruzzese + Show 6 more

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https://doi.org/10.1007/s11060-016-2297-4

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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.

Highlights

Tumors of the central nervous system (CNS) represent one of the most common causes of cancer death and account for about 1.3 % of all malignant cancer, with an incidence of 7 per 100,000 persons worldwide [1, 2]
matrix metalloproteinases -2 and -9 (MMPs)-9 can be associated with a 25-kDa protein giving a band at ~125 kDa [17, 18] and can form a complex with its endogenous inhibitors TIMP-1 giving a band at ~140 kDa [19]
There is a great interest in identifying reliable blood biomarkers that could support the management of brain tumors, e.g. facilitating neuro-radiological differential diagnosis at initial presentation, planning of surgical interventions and/or monitoring of the disease course [21, 22]

Summary

Introduction

Tumors of the central nervous system (CNS) represent one of the most common causes of cancer death and account for about 1.3 % of all malignant cancer, with an incidence of 7 per 100,000 persons worldwide [1, 2]. CNS tumors consist of a heterogeneous group of neoplasms, including different variant of primary brain tumors (glial or nonglial, benign or malignant) and metastatic neoplasms [3, 4]. Metastatic brain tumors include malignant tumors that arise elsewhere in the body (such as the breast or lungs) and migrate to the brain, usually through the bloodstream. The number of primary and metastatic brain tumors is steadily climbing, whereas mortality rate for most tumor types have remained essentially unchanged. The main diagnostic tools for both primary and metastatic CNS tumors are the anamnestic neurological examination, the imaging tests, such as conventional magnetic resonance (MRI) and computerized tomography (CT) Patients with high grade glioma usually have the worst prognosis with a median survival of 12 months even after surgical resection, radiation therapy and chemotherapy [5].

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