Activity of type IV collagenases in benign and malignant breast disease

Davies, Bernard; Miles, D. W.; Happerfield, Lisa; Naylor, M. Stuart; Bobrow, L.; Rubens, Robert; Balkwill, Frances R.

doi:10.1038/bjc.1993.207

Cited by 308 publications

(185 citation statements)

References 22 publications

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“…Furthermore, in line with several studies suggesting stromal macrophages and tumour-infiltrating neutrophils as major sources of MMP-9 in invasive cancers, e.g. in colon (Nielsen et al, 1996;Pyke et al, 1993), breast (Davies et al, 1993a), and bladder cancer (Davies et al, 1993b) and in ovarian carcinoma (Naylor et al, 1994), we detected MMP-9 immunoreactivity in neutrophils and monocyte-macrophage-like cells both in stromal and epithelial areas. This is in contrast to the findings of Huang et al (2000), who recently demonstrated MMP-9 mRNA and protein both in stromal and neoplastic cells of ovarian carcinomas (Huang et al, 2000).…”

Section: Discussionsupporting

confidence: 91%

The levels of trypsinogen isoenzymes in ovarian tumour cyst fluids are associated with promatrix metalloproteinase-9 but not promatrix metalloproteinase-2 activation

et al. 2001

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Summary Proteolysis mediated by matrix metalloproteinases (MMPs) and serine proteinases is associated with cancer invasion and metastasis. Activation of latent proMMPs, and especially the proforms of the type IV collagen degrading gelatinases A and B (proMMP-2 and proMMP-9), is thought to be a critical step in this process. We have recently found that human tumour-associated trypsin-2 is a potent activator of proMMP-9 and it also activates proMMP-2 in vitro. Trypsinogen, MMP-2, and MMP-9 are expressed in ovarian cancer. To elucidate the function of trypsin in vivo, we studied whether high concentrations of trypsinogen-1, trypsinogen-2, their α 1 -proteinase inhibitor (API) complexes, and tumour-associated trypsin inhibitor (TATI) are associated with proMMP-2 and proMMP-9 activation in ovarian tumour cyst fluids. Zymography and immunofluorometric analysis of 61 cyst fluids showed a significant association between high trypsin concentrations and the activation of MMP-9 (P = 0.003-0.05). In contrast, the trypsin concentrations were inversely associated with the activation of MMP-2 (P = 0.01-0.02). Immunohistochemical analysis of ovarian tumour tissue demonstrated expression of trypsinogen-2 and TATI in the secretory epithelium. MMP-2 was detected both in stromal and epithelial cells whereas MMP-9 was detected in neutrophils and macrophage-like cells in stromal and epithelial areas. These results suggest that trypsin may play a role in the regulation of the MMP-dependent proteolysis associated with invasion and metastasis of ovarian cancer. 1363-1371 © 2001 Cancer Research Campaign doi: 10.1054/ bjoc.2001.1806, available online at http://www.idealibrary.com on http://www.bjcancer.com aminoterminal domain for the expression of activity (Tryggvason et al, 1987). The urokinase type plasminogen activator (uPA) -plasmin system (Mazzieri et al, 1997) and membrane type MMP-1 (MT1-MMP, MMP-14) (Sato et al, 1994;Tokuraku et al, 1995) have been suggested to represent physiological mechanisms for the control of MMP-2 and MMP-9 activity. Recent studies have shown that human trypsin-2 is more potent than plasmin and other serine proteinases in activating several MMPs, including MMP-2 and MMP-9 (Sorsa et al, 1997), and that downregulation of trypsin-2 expression and activity in colon cancer cells is associated with decreased proMMP-9 activation (Lukkonen et al, 2000).In the present study we investigated the involvement of trypsin in the activation of MMP-2 and MMP-9 in vivo by studying whether the concentrations of trypsins, trypsin-API-complexes, and TATI are associated with activation of proMMP-2 and proMMP-9 in ovarian tumour cyst fluid. Furthermore, we studied the immunohistochemical expression and localization of trypsinogen-2, TATI, MMP-2, and MMP-9 in ovarian tumours. MATERIALS AND METHODS Clinical specimensCyst fluid samples (n = 61) were obtained from 58 patients (age range 13-79 years) undergoing surgery for removal of the tumour during 1986-1998 at Helsinki University Central Hospital. Of the tumours, 41 were benign...

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Section: Discussionsupporting

confidence: 91%

The levels of trypsinogen isoenzymes in ovarian tumour cyst fluids are associated with promatrix metalloproteinase-9 but not promatrix metalloproteinase-2 activation

et al. 2001

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“…MMP-2 and MMP-9 are thought to play a role in the degradation of basement membrane collagen IV and, hence, may contribute to the invasive ability of breast cancer cells (Bae et al, 1993). In situ hybridization studies have shown that the expression of MMP-2 mRNA is mostly localized in the tumor fibroblasts, while MMP-9 mRNA was found to be expressed by epithelial cells and macrophages (Davies et al, 1993;Polette et al, 1993;Wilhelm et al, 1989;Poulsom et al, 1992;Fridman et al, 1995;Okada et al, 1995). Thus, several cellular constituents of the tumor may interact to carry out degradation of the extracellular matrix by modulating MMP expression.…”

mentioning

confidence: 99%

“…Two members of the MMP family, the 72-kDa (MMP-2, gelatinase A) and 92-kDa (MMP-9, gelatinase B) proteinases, have been shown to be highly expressed in breast tumors in both the stroma and the cancer cells (Monteagudo et al, 1990;Davies et al, 1993;Sato and Seiki, 1993). MMP-2 and MMP-9 are thought to play a role in the degradation of basement membrane collagen IV and, hence, may contribute to the invasive ability of breast cancer cells (Bae et al, 1993).…”

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confidence: 99%

Epidermal growth factor and amphiregulin up-regulate matrix metalloproteinase-9 (MMP-9) in human breast cancer cells

1997

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The EGF family of proteins encompasses several polypeptides such as epidermal growth factor (EGF), transforming growth factor alpha (TGFa), amphiregulin (AR) and heregulin (HRG-b1). These polypeptides regulate proliferation in breast cancer cells through interaction with membrane receptors. It has been previously shown that high EGF receptor number correlates with aggressive behavior and increased metastasis in human breast cancer. In the present study, we investigated the association between EGF and EGF-like ligandinduced DNA synthesis and secretion of MMP-9 and MMP-2 in metastatic SKBR-3 and non-metastatic MCF-7 breast cancer cells. Exposure of SKBR-3 cells to EGF or AR induces expression of MMP-9 but has no effect on MMP-2 secretion. In contrast to EGF and AR, HRG had no effect on gelatinase induction. None of the EGF polypeptides had any effect on gelatinase induction in MCF-7 non-metastatic breast cancer cells. While a relatively specific inhibitor of EGF receptor tyrosine kinase, PD 153035, inhibited EGF-, AR-and HRGinduced cell proliferation, it had no effect on MMP-9 induced by EGF and AR. Experimental evidence suggests that signaling mechanisms for cell proliferation and MMP-9 induction are mediated by different pathways down-stream of EGF receptor autophosphorylation or that low levels of EGFinduced signal that escape inhibition are sufficient to induce MMP-9 but unable to support cell proliferation. In addition, our results suggest that EGF and AR may modulate invasion of metastatic breast cancer cells by increasing the expression of MMPs. Int.

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“…The results of this trial will be reported in the future. Type IV collagenase, matrix metalloproteinase (MMP) 2, and MMP 9, which are secreted by cancer cells, have been shown to play an important role in the degradation of BM (25)(26)(27)(28)(29). Expression of these enzymes by cancer cells has been found to be correlated with the malignant potential of various cancers (30 -36).…”

Section: Bm Preservationmentioning

confidence: 99%

Detection of Early Invasion on the Basis of Basement Membrane Destruction in Small Adenocarcinomas of the Lung and Its Clinical Implications

et al. 2001

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To evaluate the correlation between the degree of basement membrane (BM) preservation and clinicopathological characteristics in the replacementgrowth type (lepidic growth type) of small peripheral adenocarcinomas of the lung, the BM components of 72 surgically resected replacementgrowth type adenocarcinomas of the lung, 2 cm or less in diameter, were evaluated immunohistochemically by using a monoclonal antibody to Type IV collagen and polyclonal antibodies to 7S collagen and laminin. The tumors were classified into the following three distinctive histological types according to the condition of the elastic framework: Type I, bronchioloalveolar carcinoma without fibrotic foci; Type II, sclerosing bronchioloalveolar carcinoma without elastic framework destruction; and Type III, sclerosing bronchioloalveolar carcinoma with elastic framework destruction. The BM was well preserved in the area of bronchioloalveolar spread along fully expanded alveoli in all tumor types; however, BM preservation was significantly lost in the areas of collapsed alveoli in Type III tumors. There were no BM component staining reactions in the scarred regions of Type III tumors. In addition, lymph node metastasis was significantly greater in Type III tumors and BM-destroyed tumors. We concluded that the BM was largely destroyed by tumor cell invasion in the scarred region of Type III adenocarcinomas. Type III tumors had discontinuous BMs in the area of collapsed alveoli, indicating that this BM-destructive pattern must be the first step in tumor invasion. Type I and II tumors were concluded to be noninvasive adenocarcinomas, because their BM components were well preserved and they had a good outcome.

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Activity of type IV collagenases in benign and malignant breast disease

Cited by 308 publications

References 22 publications

The levels of trypsinogen isoenzymes in ovarian tumour cyst fluids are associated with promatrix metalloproteinase-9 but not promatrix metalloproteinase-2 activation

The levels of trypsinogen isoenzymes in ovarian tumour cyst fluids are associated with promatrix metalloproteinase-9 but not promatrix metalloproteinase-2 activation

Epidermal growth factor and amphiregulin up-regulate matrix metalloproteinase-9 (MMP-9) in human breast cancer cells

Detection of Early Invasion on the Basis of Basement Membrane Destruction in Small Adenocarcinomas of the Lung and Its Clinical Implications

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