Immunohistochemically, MT1-MMP and MT2-MMP are localized to the neoplastic astrocytes in glioblastoma samples (17/17 cases and 12/17 cases, respectively), which are also positive for MMP-2.
Finally, tissue microarray analysis of 68 GBM tissue specimens showed a significant correlation between the overexpression of IGFBP2 and elevated MMP-2 expression.
Similarly, U87MG cells engineered to overexpress TIMP-2 at the same levels as U87-C1 cells also demonstrated increased MMP-2 activation, indicating that an increase in physiological levels of TIMP-2 can promote MMP-2 activation and invasion in glioblastoma cells.
In this study we used RT-PCR, western blot and SDS-zymography to investigate the effect of resveratrol on the expression of genes and proteins involved in the extracellular matrix remodeling associated with tumor invasion in human cultured glioblastoma cells treated for 24, 48 and 72 h. We analyzed the expression of matrix metalloproteinase-2 (MMP-2), the main mediator of glioblastoma invasiveness, and the Secreted Protein Acidic and Rich in Cysteine (SPARC), involved in the regulation of cell-matrix interactions.
Moreover, the expression of MMP-2, its inhibitor TIMP-2 and the tumour invasiveness-related protein SPARC were effectively inhibited by TRAIL in glioblastoma cell lines.
Using real-time quantitative reverse transcription-PCR (RT-PCR), gelatin zymography, and immunohistochemistry assays, the expression of the gene encoding matrix metalloproteinase-2 (MMP2) in GBM cell lines grown in vitro or in intracranial xenografts in nude mice was shown to be repressed by either stable or adenoviral-mediated overexpression of PAX6.
Finally, immunohistochemical analysis of 45 human GBM specimens showed a significant correlation between FoxM1 overexpression and elevated MMP-2 expression.
This cannabinoid-induced inhibition of MMP-2 expression in gliomas (a) was MMP-2-selective, as levels of other MMP family members were unaffected; (b) was mimicked by JWH-133, a CB(2) cannabinoid receptor-selective agonist that is devoid of psychoactive side effects; (c) was abrogated by fumonisin B1, a selective inhibitor of ceramide biosynthesis; and (d) was also evident in two patients with recurrent glioblastoma multiforme.
Together, our data strongly suggest that LRP1 promotes glioblastoma cell migration and invasion by regulating the expression and function of MMP2 and MMP9 perhaps via an ERK-dependent signaling pathway.
By virtue of its restricted expression in GBM and its role in invasion, Necl-5 may be an attractive target for limiting MMP-2 production in glioblastoma, and therefore limiting dispersal.
Consistent with this idea, 39% less extracellular MMP2 was measured from knockdown cells identifying one mechanism by which calpain 2 mediates glioblastoma cell invasion.
The effect of different doses of X(-)rays on apoptosis, proliferation, epidermal growth factor receptor (EGFR) and matrix metalloproteinase (MMP-2) expression was investigated in a human glioblastoma cell line.
A significant association of MMP-2 (-1306C/T) polymorphism with GBM (P = 0.475) was not found, suggesting that MMP-2 (-1306C/T) polymorphism is not associated with increased GBM susceptibility.
We find that MMP-2 activity in human U251 GBM xenografts increases (*P=0.03) and collagen IV content decreases (*P=0.01) during vascular endothelial growth factor (VEGF-A) antibody neutralization.
Further research into the underlying mechanism demonstrated that the effects of miR-125b on the invasion of glioblastoma CD133-positive cells were associated with the alteration of the expression of MMPs (MMP-2 and MMP-9) and corresponding inhibitors (RECK and TIMP3).
These findings demonstrated that hCGβ phosphorylated ERK1/2 upregulating MMP-2 expression and activity leading to cell migration and invasion, suggesting that hCGβ, ERK1/2 and MMP-2 are the potential targets to inhibit glioblastoma invasion.
In the present study, we observed that IR (8 Gy) significantly elevated MMP-2 expression and gelatinolytic activity in 4910 and 5310 human GBM xenograft cells.
The data presented here suggest that miR-223 promotes the growth and invasion of U251 and U373 glioblastoma cells by targeting PAX6, which serves as a tumor suppressor in glioblastoma exerting the functions of inhibition of cell cycle transition, and the expression of MMP2, MMP9 and VEGFA.
A significant decline of MMP-9 and MMP-2 secretion in cultured U87MG was detected after incubation with EBB (42.9% and 73.0%, respectively) and EBB + TMZ (38.4% and 68.5%, respectively).