Possible Role of Matrix Metalloproteinase in Osteolytic Intracranial Meningiomas

Abstract

Objective : Abnormalities of the bone are frequently encountered in patients with meningioma, and hyperostosis and endostosis are common bone alterations in these tumors. Extensive bony destruction is very unusual in patients with meningioma. We report six cases of intracranial meningioma associated with an osteolytic lesion of the skull and discuss the underlying mechanisms that may be responsible for bone destruction in patients with meningioma. Methods : Six patients were classified into three groups, severe, moderate and mild, according to the degree of osteolytic bony destruction. The tumor was classified as intracranial or extracranial, depending on its location. We investigated the potential role of matrix metalloproteinase (MMP) in meningioma-associated osteolysis. The levels of MMP expression were determined by gelatin zymography, reverse transcriptionquantitative PCR analysis (RT-PCR) and immunohistochemical analysis. Results : Complete surgical removal of the lesion was performed in each patient. Histological examination revealed benign meningioma in four cases, and two cases of atypical meningioma. Patients did not have a poor prognosis except one case of recurred atypical meningioma. Gelatin zymography and RT-PCR detected high levels of MMP-2 in almost all extracranial masses in comparison with the intracranial masses and MMP-9 in two. There was no difference in the severity of bone destruction. Immunohistochemical analysis revealed MMP-2 expression in the vicinity of the bone destruction, and a few MMP-9-positive stainings were observed. Conclusion : Osteolysis of the skull in patients with meningiomas might not be indicative of malignant pathological features and poor prognosis. Invasion to the extracranial portion and osteolysis might be associated with MMP-2 expression in meningioma.

Magnetic resonance imaging and computed tomographic characteristics of a glioma causing calvarial erosion in a dog

“…The pathophysiology of glioma‐associated skull osteolysis is unknown. In humans, the main proposed mechanisms that could lead to skull osteolysis include: (1) direct invasion of tumor cells into the skull bone; (2) tumor's pressure to the inner table of the skull; and (3) destruction caused by proteolytic enzymes secreted by the tumor cells (i.e., matrix metalloproteinases) . Tumor cells invading the skull surrounding the glioma were not detected on histopathogy, thus this mechanism is thought to be less likely in this case.…”

“…The loss of subarachnoid space because of mass effect, and the direct contact of the brain with the skull could cause a focal increase of pressure that lead to erosion of the inner table of the skull over time. Matrix metalloproteinases are proteolytic enzymes located in the cytoplasm of neoplastic cells that have the ability to break down basal membranes and connective tissue allowing growth, expansion, and metastasis of the tumor . An immunohistochemical study of canine and feline meningiomas revealed widespread expression of matrix metalloproteinase 2 and matrix metalloproteinase 9 enzymes, and expression of matrix metalloproteinase 2 in human meningiomas seems to be related to invasion of the skull .…”

“…Matrix metalloproteinases are proteolytic enzymes located in the cytoplasm of neoplastic cells that have the ability to break down basal membranes and connective tissue allowing growth, expansion, and metastasis of the tumor . An immunohistochemical study of canine and feline meningiomas revealed widespread expression of matrix metalloproteinase 2 and matrix metalloproteinase 9 enzymes, and expression of matrix metalloproteinase 2 in human meningiomas seems to be related to invasion of the skull . The enzymes matrix metalloproteinase 2 and matrix metalloproteinase 9 are also the most common matrix metalloproteinases expressed in humans gliomas and their presence is considered critical for tumor invasion .…”

Proteins involved in regulating bone invasion in skull base meningiomas

“…The biological role and functional contribution of MMPs is complex and their role in meningiomas is far from established. Previous studies have focused on establishing the role of MMP2 in meningiomas, in particular as it relates to tumor recurrence, brain invasion, and peritumoral edema, and the data is conflicting [10, 19, 21, 23, 24, 26, 28–31, 48]. Though some studies found higher MMP2 expression levels in recurrent meningiomas [28, 48], others have found no association between meningioma grade and MMP2 levels [29].…”

“…Though some studies found higher MMP2 expression levels in recurrent meningiomas [28, 48], others have found no association between meningioma grade and MMP2 levels [29]. No correlation between MMP2 expression level and brain-invasive potential of meningiomas has been found to date [23, 24, 26]. Studies focused on the predictive potential of MMP2 on meningioma peritumoral edema have been contradictory, with Paek et al [30] suggesting a positive association, whereas Panagopolous et al [31] noted no such association.…”