Our studies revealed that both MMP-2 and -9 immunoreactivities (IRs) were upregulated in 13 of 25 (52 %) and 19 of 25 (76 %) GBMs, respectively, and the extent of the increase was highly significant with respect to controls (p < 0.001).
In addition, our data suggest that MMP2 and E-cadherin, a key factor in epithelial-mesenchymal transition (EMT), are involved in the miR-633/TGF-β1-mediated metastasis of glioblastoma.
Tissue samples from 89 patients diagnosed with diffuse astrocytoma, anaplastic astrocytoma and glioblastoma were stained immunohistochemically using a monoclonal MMP-2 antibody.
Western blotting was used to determine the protein levels of TSHZ3 and MMP2 in glioblastoma cell lines and Matrigel invasion assay to examine the role of miR-338-5p in cell invasiveness.
Among these MMPs, gelatinases (MMP-2 and MMP-9) and its activator MMP-14 are known to play a key role in tumour angiogenesis and the growth of many cancers such as glioblastoma multiforme (GBM), an aggressive malignant tumour of the brain.
We further elucidate the effects of inhibition of ECM remodeling-related enzymatic activity (Matrix metalloproteinase (MMP) 2/9, hyaluronan synthase (HAS)) on GBM cell invasion.
Tumor growth rate and final tumor weight were significantly increased in the animals with the glioblastoma derived from transfected U87-H4645 cells, compared to untransfected and vector control (p<0.01). mRNA expression of β-catenin, CD44, ICAM-1, and MMP-2 in the glioblastoma derived from the transfected U87-H4645 tumors was significantly increased compared with tumors derived from untransfected and vector-control U87 cells (p<0.01).
Activation of PI3K/AKT signaling prevented the suppressive effects of RWDD3 downregulation on glioblastoma cell proliferation and migration, concurrent with increased protein levels of MMP2 and MMP9.
In this study, utilizing an array of techniques, including gelatin matrix degradation assays, we show that GBM cell lines can form functional gelatin matrix degrading invadopodia and secrete matrix metalloproteinase 2 (MMP-2), a known invadopodia-associated matrix-degrading enzyme.
Zymography analysis also revealed that the activities of MMP-2 and MMP-9 of GBM cells were significantly inhibited in response to 100, 200, or 300 μM naringenin treatment.
We analysed the transcript expression of CLEC5A in glioblastoma by accessing The Cancer Genome Atlas (TCGA). qRT-PCR was performed to detect the RNA expression of genes in cells and tissues, and Western blot was used to measure the protein levels (Cyclin D1, Bcl-2, BAX, PCNA, MMP2, MMP9, Akt and Akt phosphorylation) in tissues and cells.
Thus preclinical validation of molecular interaction between diosgenin and NFE2L2 down-regulating MMP-2, EMT markers and promoting apoptosis, offers rationale for new therapeutic horizons in the field of glioblastoma management.
We showed a 20-fold upregulation of A<sub>2B</sub> AR on GB compared with sham, and its activation induced matrix metalloproteinase-2, which enhanced GB pathogenesis.
GBM cell lines capable of forming caveolae expressed more uPA and matrix metalloproteinase-2 (MMP-2) and/or -9 (MMP-9) and were more invasive than GBM cells devoid of caveola-forming proteins.
The association of HSP27 with MMP-2 and MMP-9 proteins along with the identified interacting stretch has the potential to contribute towards drug development to inhibit GBM infiltration and migration.
Downregulation of the miR-221/222 cluster diminished the invasion, migration, proliferation, and angiogenesis with reduced protein levels of matrix metalloproteinase-2 (MMP-2), MMP-9, and vascular endothelial growth factor in glioblastoma cells.