The expression of matrix metalloproteinase-2 and-9 in human gliomas of different pathological grades

Abstract

Matrix metalloproteinases (MMPs) have been implicated to play a critical role in glioma invasiveness. In this study, we aimed to investigate the expression of MMP-2 and MMP-9 in human gliomas of different degrees of malignancy, and evaluated the correlation between MMP-2 and MMP-9 expression in gliomas. The samples from 65 cases of glioma were divided into four groups according to the WHO classification: there were 16 cases of grade I, 17 cases of grade II, 20 cases of grade III, and 12 cases of grade IV. Normal brain samples served as the control group, and biopsy specimens were obtained from 8 glioma patients with a needle placed into the adjacent brain 1 cm from the margin after tumor resection. All the samples were stained with hematoxylin and eosin and immunohistochemistry. A computer-aided image-analysis system was employed to measure the integral optical density (IOD) of positive slides. No positive staining was found in the control group. The positive staining was localized in the cytoplasm of glioma cells, the extracellular matrix (ECM), the basement membrane (BM), and the endothelial cells of blood vessels. Positive staining rates increased significantly when the degree of malignancy of gliomas was elevated. The IOD value of MMP-2 and MMP-9 also indicated that the intensity of MMP-2 and MMP-9 expression was elevated significantly with the degree of malignancy of the gliomas. There was a positive correlation between MMP-2 and MMP-9 expression in gliomas. Glioma invasion and angiogenesis were particularly seen in the biopsied tissues, and MMP-9 immunostaining seemed to be much more intense and extensive than MMP-2 immunostaining in these samples. These results suggest that MMP-2 and MMP-9 staining in gliomas is localized in the cytoplasm of tumor cells, BM, and endothelial cells, and that MMP-2 and MMP-9 together play an important role in the invasiveness of gliomas, mediating the degradation of the ECM and angiogenesis. MMP-2 and MMP-9 could be molecular targets in the treatment of malignant glioma.

Extracellular Matrix Microenvironment in Glioma Progression

“…The glioma vasculature as well as infiltrating inflammatory cells, which form a portion of the glioma mass have been implicated in MMP expression (VanMeter et al 2001). Strong gelatinase expression correlates with tumor grade (Forsyth et al 1999, Wang et al 2003. Intracranial implantation of glioblastoma cells in nude mice resulted in increased levels of MMP-9 during growth (Sawaya et al 1998, Chintala et al 1999).…”

Effect of resveratrol on matrix metalloproteinase-2 (MMP-2) and Secreted Protein Acidic and Rich in Cysteine (SPARC) on human cultured glioblastoma cells

“…Gelatinases, particularly matrix metalloproteinase-2 (MMP-2), can be considered the prime factor in glioma invasiveness, since it can break down the basement membrane ECM components such as collagen type IV and laminin. MMP-2 expression also correlates with the progression and the degree of malignancy of gliomas [8,9].…”

Adenovirus-mediated transfer of siRNA against MMP-2 mRNA results in impaired invasion and tumor-induced angiogenesis, induces apoptosis in vitro and inhibits tumor growth in vivo in glioblastoma

“…It has been shown that MMP-2 is localized in both tumor and vasculature cells, indicating multiple roles for this molecule in tumor progression, including angiogenesis (Sawaya et al, 1996;Forsyth et al, 1999). MMP-2 expression is also known to associate with tumor invasion, angiogenesis, metastasis and recurrence (Wang et al, 2003;Chambers andMatrisian, 1997, Komatsu et al, 2004).…”