Matrix metalloproteinases (MMP), such as 72 kDa type IV collagenase (MMP-2) and 92 kDa type IV collagenase (MMP-9), play an important role in tumor invasion and metastasis.
Restored expression of RECK in malignant cells resulted in suppression of invasive activity with concomitant decrease in the secretion of matrix metalloproteinase-9 (MMP-9), a key enzyme involved in tumor invasion and metastasis.
The gelatinases B (MMP-9) and A (MMP-2) are 2 members of the matrix metalloproteinase (MMPs) family which are expressed in human cancers and thought to play a critical role in tumor cell invasion and metastasis.
Enhanced mRNA expression of gelatinase A or gelatinase B and of matrilysin showed trends toward presence of capsular invasion (P = 0.078) and intrahepatic metastasis (P = 0.064), respectively.
Although the basement membrane-degrading enzymes, MMP-2 and MMP-9, have been given considerable attention for their roles in invasion and metastasis, the interstitial collagenases, a subfamily of MMPs that cleaves the stromal collagens types I and III, have received relatively little recognition for their part in these processes.
We found earlier that over-expression of bcl-2 in a human breast-cancer cell line (MCF7(ADR)) enhances its tumorigenicity and metastatic potential by inducing metastasis-associated properties such as increased secretion of the matrix metalloproteinase-9 (mmp-9).
These results demonstrate that IL-8 expression regulates angiogenesis in prostate cancer, in part by induction of MMP-9 expression, and subsequently regulates the growth and metastasis of human prostate cancer.
The increase in MMP-9 production by N-cadherin-expressing cells in response to a growth factor may endow them with a greater ability to penetrate matrix protein barriers, while the increase in their adherence to endothelium may improve their ability to enter and exit the vasculature, two properties that may be responsible for metastasis of N-cadherin-expressing cells.
Systemic therapy with IFN-alpha (10,000 units s.c. daily) decreased the expression of MMP-9, increased expression of E-cadherin, reduced tumor volume, and inhibited metastasis.
Since MMP-9 is tightly associated with invasion/metastasis and angiogenesis, our studies suggest that blocking heregulin-beta1-mediated activation of MMP-9 by inhibiting the related signaling pathways may provide new strategies for inhibition of cancer metastasis and angiogenesis.
We undertook a study to determine whether the KiSS-1 gene, previously shown to suppress cancer spread (metastases), negatively regulates MMP-9 expression.
Given the spectrum of key molecules that can be cleaved by LE and that LE and MMP-9 are involved in the invasive behavior of normal or transformed leukocytes, our results raise the hypothesis that LE plays a crucial role in the multistep processes of inflammation and lymphoma metastasis.
Multivariate analysis of disease-free survival showed that the ratio of MMP-9 to E-cadherin (P = 0.012) and the expression level of bFGF expression (P = 0.045), were independent predictors for the development of metastases.
MMP-9 is a human protease and is involved in a variety of physiological and pathological matrix degrading processes, including tissue invasion of metastases and opening of the blood-brain barrier.
We extended these studies and more recently observed increased expression of genes related to angiogenesis such as vascular endothelial growth factor (VEGF) and those related to metastasis such as matrix metalloproteinases (MMP)-2 and MMP-9 in prostate cancer of TRAMP mice.
NF-kappaB-mediated expression of genes involved in angiogenesis (IL-8, VEGF), and invasion and metastasis (MMP9, uPA, uPA receptor) may further contribute to the progression of prostate cancer.