The expression levels of associated genes, including epithelial cadherin (E‑cadherin), metalloproteinase inhibitor 2 (TIMP‑2), metastasis associated 1 (MTA1) and matrix metallopeptidase 2 (MMP2), were analyzed using reverse transcription‑quantitative polymerase chain reaction analysis and western blotting.
Three types of membrane type-matrix metalloproteinases (MT-MMPs) have been identified as activators of pro-MMP2 (gelatinase A/72-kilodalton Type IV collagenase), which is believed to be crucial for tumor invasion and metastasis.
The diminishment of metastasis and invasion is associated with down-regulation of genes including MMP-2, S100A, LAMA4, and HDAC10, as well as up-regulation of genes such as MTSS1 and FSTL1 as revealed by gene chip analysis.
Consistent with its regulatory role in NF-κB pathway, knockdown of DEPDC1 caused significant upregulation of A20 and downregulation of mutiple NF-κB downstream target genes implicated in proliferation and tumorigenesis (c-Myc, BCL2, CCND1, CCNB1 and CCNB2), and metastasis (MMP2, MMP9, ICAM1, vimentin, Twist1).
The effect of ATO on the transcriptional level of genes involved in survival (Bcl-2, Bax and Survivin), self-sufficiency in growth signals (c-Myc, ARF, Cdc25A, p53 and Bax), immortalization (hTERT) and invasion and metastasis (MMP-2 and MMP-9, uPA and uPAR and E-cadherin) was more pronounced in MCF7-hGH compared with its parental MCF-7 line.
However, no significant association was demonstrated between the MMP2 polymorphism and risk of metastasis of the cancer at the time of diagnosis, with the odds ratio being 0.90 (95% confidence interval 0.36-2.20) for the CC genotype.
These inhibitory effects were accompanied by mechanistic down-regulation of the protein levels of inflammatory enzymes (inducible nitric oxide synthase, iNOS and cyclooxygenase-2, COX-2), metastasis (matrix metallopeptidase-2, MMP-2 and MMP-9), angiogenesis (vascular endothelial growth factor, VEGF), and proliferative molecules, as well as by the induction of apoptosis in prostate tumors.
We used the human, androgen-sensitive prostate carcinoma cell line LNCaP in coculture with the human osteosarcoma cell line OHS to experimentally address the possibility of androgen-dependent regulatory effects on the functional MT1-MMP/TIMP-2/MMP-2 complex upon interaction between prostate carcinoma and osteoblastic cells in metastasis of prostate cancer to bone.
There is also a significant correlation between the expression levels of CXCR4-CXCL12 axis and metastasis-related genes (E-cadherin and MMP2) in tumor samples with advanced stages of metastasis.
In particular, gelatinases, matrix metalloproteinase-2 (MMP-2) and MMP-9, have been implicated to play a role in colon cancer progression and metastasis in animal models and patients.
These findings indicate a new regulatory mode, whereby miR‑29b, which is inhibited by its upstream transcription factor SRF, was able to promote its direct target MMP2 leading to NSCLC invasion and metastasis.
Together, these findings indicate that OPN enhanced HCC cells invasion through interaction with its receptor CD44v6 and increased MMP-2 and uPA expressions, providing at least one mechanism for OPN-mediated HCC progression and metastasis.
Furthermore, we show that the invasive cell populations express the metastasis-associated proteins matrix metalloproteinase MMP-2, CD44, and integrins alpha(v)beta3 and alpha6.
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.