Positive signal for 92-kDa type IV collagenase mRNA was detected in eosinophilic granulocytes within inflammatory infiltrates surrounding the tumor nodules.
Zymography revealed higher levels of MMP-9 activity in the ovarian cancer biopsy samples than in other cancers studied, but in contrast to our previous observations in breast and bladder cancer, there was no correlation between MMP levels and tumor grade.
In liver metastases, MMP-9 localised within peritumour stroma or at the interface between the tumour stroma and normal liver, whereas TIMP-1 mRNA was located throughout the malignant tumour stroma.
We conclude that, in human pancreatic cancer, MMP-2, MMP-9, TIMP-1 and TIMP-2 may be involved in processes leading to the strong desmoplastic reaction observed in these tumors.
Our results highlight a positive correlation between up-regulated beta3 integrin and MMP-9 expression in human HT-144 melanoma cell tumors grown in nude mice.
We have recently demonstrated elevated activity of the 92 kDa type IV collagenase (MMP-9) in human glioblastoma and in the present study examine the relative amounts of MMP-9 protein and mRNA in human gliomas and as well as the distribution of MMP-9 in human glioma tumors in vivo.
We used northern blot analysis of RNA from fresh-frozen tumour specimens to study the patterns of expression of genes for proteolytic enzymes (cysteine proteinase cathepsin L and aspartyl proteinase cathepsin D; matrix metalloproteinases MMP-9 and MMP-2), tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2, and TP53.
The ratio of type IV collagenase expression (mean of the expression of MMP-2 and MMP-9) to E-cadherin expression (MMP:E-cadherin ratio) at the periphery of the tumors was significantly higher in patients with recurrent disease (4.7 +/- 2.1) than in patients who were disease free (2.3 +/- 1.7; P = 0.0008).
The daily s.c. administrations of 5,000 or 10,000 units IFN-alpha-2a produced maximal inhibition of bFGF and MMP-9 expression (mRNA and protein), maximal reduction in tumor vessel density, and maximal reduction in serum levels of bFGF.
MCF7Jun cells exhibit increased cellular motility, increased expression of a matrix degrading enzyme MMP-9, increased in vitro chemoinvasion and tumor formation in nude mice in the absence of exogenous estrogens.
Regardless of Gleason score, the highest expression level for E-cadherin was found in the center or perineural area of the tumors, whereas the highest expression levels for MMP-2 and MMP-9 were associated with the invasive edge.
On the other hand, the latent form of MMP-9 was found in almost equal amounts both in tumor and normal liver samples, but its active form was present only in HCC.
As MMP7 and MMP9 have been shown to generate angiostatin from circulating plasminogen, and angiostatin acts as a potent inhibitor of endothelial cell proliferation, we determined whether tumor vascularization was altered in the alpha1-null mice.
Whether aspirin and sodium salicylate could reduce invasiveness and whether LMP1 could enhance MMP-9 expression in tumors grown in nude mice were also tested.
In contrast, the ratio between expression of type IV collagenases (mean of the expression of MMP-2 and MMP-9) and E-cadherin, the MMP:E-cadherin ratio (measured at the periphery of each tumor), was significantly higher in patients with recurrent disease than in patients who remained disease free (P = 0.00003).
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.
Expression of the growth-promoting integrin alphavbeta6 in colon cancer cells induces gelatinase B secretion and activation, the inhibition of which abolishes alphavbeta6-mediated tumour cell growth within a collagen matrix.