Possible role of matrix metalloproteinases (MMPs) in hyperostosis of intracranial meningiomas.
OBJECTIVE
Although bone invasion and hyperostosis are common phenomena in patients with intracranial meningiomas, the basic pathomechanism is not fully understood. Based on an immunohistochemical study of surgically resected samples with hyperostosis, we postulate a possible mechanism of hyperostosis in patients with intracranial meningiomas.


METHODS
Forty-six meningiomas were evaluated in this study. Twenty-six meningiomas associated with hyperostosis specimens served as the study group, and 20 meningiomas without any bony changes served as controls. An immunohistochemical staining technique was used to detect the expression of matrix metalloproteinase (MMP)-2, -9, and -13, membrane type (MT)1-MMP, estrogen receptor (ER), and progesterone receptor (PR) in the main tumor and hyperostotic portions of the studied samples.


RESULTS
In the non-hyperostosis group, expression of MMP-13, MT1-MMP, and ER was significantly less than in the main tumor portion of hyperostotic meningiomas, while there was no difference in the expression of MMP-2 and -9 and PR in the main tumor between the two groups. In the hyperostosis group, the immunoreactivity of MMP-2 in the hyperostotic portion revealed a higher pattern of expression than the main tumor (p < 0.002). The expression of MMP-9, MT1-MMP, ER, and PR had relatively positive immunoreactivity in the main tumor portion (P < 0.05).


CONCLUSIONS
Increased expression of MMP-13 and MT1-MMP in the tumor portion of hyperostosis of meningiomas might contribute to the initiation of osteolysis. Activated MMP-2 in hyperostotic lesions may change the physiological metabolism of the skull bone, thus playing an important role in hyperostosis formation.
Department of Brain Tumor Research Laboratory, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, Gwangju, Korea.
Jian
J
Pei
Shin
S
Jung
Shu-Guang
SG
Jin
Kyung-Sub
KS
Moon
Min
M
Wen
Song-Yuan
SY
Li
Woo-Youl
WY
Jang
Hyang-Hwa
HH
Ryu
Kyung-Hwa
KH
Lee
In-Young
IY
Kim
Tae-Young
TY
Jung
D014408:Biomarkers, Tumor / Q000502:physiology; D005260:Female; D006801:Humans; D015576:Hyperostosis / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000502:physiology; D053511:Matrix Metalloproteinase 14 / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000502:physiology*; D008577:Meningeal Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D008579:Meningioma / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D010014:Osteolysis / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D012886:Skull / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology
D014408:Biomarkers, Tumor; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14