These results suggest that interstitial collagenase gene activation in the tumor stroma, especially eosinophils, may have an important role in tumor invasion and metastasis.
These findings indicate that expression of the MMP-1 gene is greater in stromal cells that are closely associated with cancer cells, suggesting a pathophysiological role of MMP-1 in the invasion and metastasis of cancer cells.
Expression of MMP-1 mRNA was not related to the grade of malignancy, and appeared in stromal eosinophils, suggesting to us that it is involved in a remodelling process in the reaction of the host to tumour invasion.
These findings indicate that the stromal cells may play an important role in the expression of MMP-1, and suggest a pathophysiological role for MMP-1 in the invasion and metastasis of gastric cancer.
Since MMP-1, MMP-3 and MMP-9 play important roles in tumor invasion and TGF-beta and VEGF are involved in tumor angiogenesis, hypothemycin is considered to be an example of a new class of antitumor drugs, whose antitumor efficacy can be at least partly attributed to inhibition of Ras-inducible genes.
Although MMP-1 may be just one of the many factors responsible for tumor cell invasion, the present findings demonstrating the possibility, at least in vitro, of repressing MMP gene expression may have important clinical ramifications.
In addition, among the pancreatic carcinomas, we compared MMP-1 expression in relation to the degree of differentiation, lymph node metastasis, and depth of invasion of the carcinoma.
IFN-gamma abolished the enhancement of MMP-13 and MMP-1 expression by transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha), and inhibited invasion of A-5 cells through type I collagen.
This further substantiates the important role of tumor stroma in regulating the expression of matrix metalloproteinase 1, a major matrix-degrading proteinase implicated in tumor invasion.
Recent studies have found that overexpression of MMP-1 is associated with the initial stages of cancer development in addition to promoting cellular invasion; however, preexisting oncogenic mutations or chemical carcinogens are required to initiate tumorigenesis as well.
Since matrix-degrading proteases secreted by stromal fibroblasts contribute significantly to tumor invasion, we analyzed the stromal expression of 2 matrix metalloproteinases (MMP-1 and -9) and of one of their regulators, the Ets 1 transcription factor, by both immunohistochemistry and in situ hybridization in sporadic colorectal carcinomas and HNPCC tumors.
In fact, our data show that incubation of PTHrP [67-86]-amide-treated cells with either antisense hsbp1-oligonucleotide or geldanamycin, an hsp90-inactivating antibiotic, results in downregulation of uPa and upregulation of MMP-1, and in a prominent inhibition of cell invasion in matrigel-containing Transwell chambers.
We previously reported that an elevated level of matrix metalloproteinase-1 (MMP-1) gene expression in patients with chondrosarcoma has a strong statistical correlation with recurrence and in vitro invasion.
In reverse transcription-polymerase chain reaction series of genes relating to motility and invasion, we demonstrated striking evidence that matrix metalloproteinase (MMP-1), MMP-2, MMP-7, and MT1-MMP expressions were strongly upregulated by Snail.
The purpose of present study is to determine the involvement of c-Jun in matrix metalloproteinase-1 (MMP-1) expression, which is previously reported by us to be expressed only in the early stage of human HCC showing stromal invasion.
Matrix metalloproteinase-1 (MMP-1) plays a key role in cancer invasion and metastasis by degradation of extracellular matrix (ECM) and basement membrane barriers.