Our results suggested that HIF-1α binds to AEG-1 promoter to upregulate its expression, which was correlated with metastasis in ovarian cancer by inducing the expression of MMP2 and MMP9 as well as inhibiting expression of E-cadherin and β-catenin.
Furthermore, expression of matrix metalloproteinases 2/9 (MMP2 and MMP9) was positively related with PDGF-D, indicating their involvement in the invasion and metastasis of ovarian cancer.
We have related these data to expression of some of the controlling elements of the enzymes, namely tissue inhibitors of metastasis (TIMPs) and tumor necrosis factor (TNF). mRNA for MMP-2 was found in the majority of cases and localized to stromal areas with maximal expression adjacent to neoplastic areas.
Moreover, these cells exhibited high metastasis in mice, and p-p65, MMP-2, and MMP-9 expression levels were elevated in the primary tumor and liver metastases.
Our results showed, reduction in MMP-2 (p=0.08), MMP-9 (p=0.03), CCL22 (p=0.003) and TGFβ1 (p=0.1) gene expression and Tregs frequency (p=0.01) which play a main role in the development of chronic inflammation, angiogenesis, tumorigenesis and metastasis.
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.
Our results imply that MMP-2 and/or MMP-9 play an important role in invasion and metastasis in tongue cancer, and that analysis of MMP expression and/or activity in primary tumours may have a predictive value for the actual or potential presence of cervical metastases.
In addition, scratch and invasion assay showed that HBC also dose-dependently suppressed migration and invasion capacities of highly metastatic HCC HepG2 cells through down-regulated the expression of tumor metastasis related proteins MMP-2 and MMP-9, significantly better than SAHA.
Thymoquinone inhibits metastasis of renal cell carcinoma cell 786-O-SI3 associating with downregulation of MMP-2 and u-PA and suppression of PI3K/Src signaling.
That observation was supported by the findings that p202-expressing tumors showed reduced expression of angiogenic markers, such as interleukin 8 and vascular endothelial growth factor, and p202-expressing pancreatic cancer cells have reduced level of matrix metalloproteinase-2 activity, a secreted protease activity important for metastasis.
Using pharmacological inhibitors, siRNAs, and blocking antibodies, we demonstrated that the MMP-1 and MMP-2 matrix metalloproteinases, known to participate in late stages of cancer invasion and metastasis, are responsible for this enhancement of early migratory capacity.
Western blotting results revealed that knocking down ZEB2-AS1 could inhibit cell invasion and metastasis by suppressing the epithelial to mesenchymal transition (EMT) as well as the expressions of matrix metallopeptidase-2 (MMP-2) and MMP-9 in AGS cells.
Matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9) are involved in the breakdown of extracellular matrix in normal physiological processes as well as in disease processes, such as cancer metastasis.
The expression levels of the cell apoptosis and tumor metastasis associated proteins B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein, E‑cadherin, Twist, matrix metalloproteinase (MMP)‑9 and MMP2 were measured via western blotting.
Consistent with these findings, SCCRO and MMP2 are coexpressed (P<0.0001; r(2)=0.58; 95% confidence interval, 0.46-0.69) in primary (upper aerodigestive tract) carcinomas (n=89), and this coexpression is associated with an increased prevalence of regional nodal metastasis (P=0.04; relative risk, 1.53).
EZH2 and MMP2 proteins were found to be expressed at higher levels in tissues from patients where RCC had metastasized to the bone as compared with those in RCC patients without metastasis, whereas there was no significant difference in the expression of TIMP2 protein between the two tissues.
These findings indicate that the activity of the gelatinases MMP-2 and -9 affects the tumor progression and metastasis of patients with CRC, providing a potential novel approach for determining the prognosis of CRC.