Activation of ProMMP‐9 by a Plasmin/MMP‐3 Cascade in a Tumor Cell Model: Regulation by Tissue Inhibitors of Metalloproteinases

Hahn-Dantona, Elizabeth; RAMOS-DeSIMONE, Noemi; Sipley, John; Nagase, Hideaki; French, Deborah L.; Quigley, James P.

doi:10.1111/j.1749-6632.1999.tb07696.x

Cited by 85 publications

(52 citation statements)

References 37 publications

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“…A functional role for uPA is to convert plasminogen to plasmin, a serine protease capable of degrading key ECM components and activating other zymogen proteases such as pro-MMP-9 and pro-MMP-3 (Davis et al, 2001;Hahn-Dantona et al, 1999;RamosDeSimone et al, 1999). Correlations have been made between expression of individual MMPs (e.g.…”

Section: Introductionmentioning

confidence: 99%

Caveolin-1 mediates the expression and localization of cathepsin B, pro-urokinase plasminogen activator and their cell-surface receptors in human colorectal carcinoma cells

Cavallo-Medved

Mai

Dosescu

et al. 2005

Journal of Cell Science

117

100

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Cathepsin B and pro-urokinase plasminogen activator (pro-uPA) localize to the caveolae of HCT 116 human colorectal carcinoma cells, an association mediated by active K-RAS. In this study, we established a stable HCT 116 cell line with a gene encoding antisense caveolin-1 (AS-cav-1) to examine the effects of caveolin-1, the main structural protein of caveolae, on the expression and localization of cathepsin B and pro-uPA, and their cell-surface receptors p11 and uPA receptor (uPAR), respectively. AS-cav-1 HCT 116 cells secreted less procathepsin B than control (empty vector) cells as measured by immunoblotting and pepsin activation of the proenzyme. Expression and secretion of pro-uPA was also downregulated in AS-cav-1 HCT 116 cells. Localization of cathepsin B and pro-uPA to caveolae was reduced in AS-cav-1 HCT 116 cells, and these cells expressed less total and caveolae-associated p11 and uPAR compared with control cells. Previous studies have shown that uPAR forms a complex with caveolin-1 and β1-integrin, and we here show that downregulation of caveolin-1 also suppressed the localization of β1-integrin to caveolae of these cells. Finally, downregulation of caveolin-1 in HCT 116 cells inhibited degradation of the extracellular matrix protein collagen IV and the invasion of these cells through Matrigel. Based on these results, we hypothesize that caveolin-1 affects the expression and localization of cathepsin B and pro-uPA, and their receptors, thereby mediating cell-surface proteolytic events associated with invasion of colon cancer cells.

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Section: Introductionmentioning

confidence: 99%

Caveolin-1 mediates the expression and localization of cathepsin B, pro-urokinase plasminogen activator and their cell-surface receptors in human colorectal carcinoma cells

Cavallo-Medved

Mai

Dosescu

et al. 2005

Journal of Cell Science

117

100

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“…By cleavage of plasminogen and collagen XVIII, MMP12 is one of the most effective producers of the angiogenesis inhibitors angiostatin and endostatin [8]. In addition, it has an influence on the plasmin levels and subsequent activation of MMPs like MMP3 and MMP9 [9]. MMP2, also known as gelatinase A, is involved in migration and invasion processes and also seems to have influence on chemotherapy response.…”

mentioning

confidence: 99%

Single nucleotide polymorphisms in matrix metalloproteinase genes and lung cancer chemotherapy response and prognosis

Scherf

Dally²,

Müller³

et al. 2009

European Respiratory Journal

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The prognosis for lung cancer patients treated with chemotherapy is poor. Single nucleotide polymorphisms (SNPs) in matrix metalloproteinase (MMP) genes could influence treatment outcome by altering apoptotic pathways. Eight SNPs with known or suspected phenotypic effect in six genes (MMP1, MMP2, MMP3, MMP7, MMP9 and MMP12) were investigated.For 349 Caucasian patients with primary lung cancer, receiving first-line chemotherapy, three different endpoints were analysed: response after the second cycle, progression free survival (PFS) and overall survival (OS).The prognostic value of the SNPs was analysed using multiple logistic regression for all patients and histology-, stage-and treatment-specific subgroups. Hazard ratio estimates for PFS and OS were calculated using Cox regression methods.None of the investigated polymorphisms modified response significantly in the whole patient population.However, tumour stage IIIB variant allele carriers of MMP2 C-735T showed a significantly worse response. PFS was significantly prolonged in MMP1 G-1607GG variant allele carriers and OS in small cell lung cancer patients carrying the MMP12 A-82G variant allele.In conclusion, this study identified SNPs in MMP1, MMP2, MMP7 and MMP12 for further investigation as possible predictors of chemotherapy outcome in lung cancer patients.

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“…uPA converts plasminogen to plasmin (21), another serine protease with a broad spectrum of substrate specificity and capable of cleaving fibrin in thrombolysis (22,23), degrading key extracellular matrix (ECM) components (24,25), and activating other zymogen proteases. For example, plasmin is shown to be indirectly involved in pro-MMP-9 activation by activating pro-stromelysin 1 (26)(27)(28). Thus, control of uPA activity may affect MMPdependent proteolysis.…”

mentioning

confidence: 99%

Maspin expression inhibits osteolysis, tumor growth, and angiogenesis in a model of prostate cancer bone metastasis

Cher

Biliran

Bhagat

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

147

150

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Emerging evidence indicates that tumor-associated proteolytic remodeling of bone matrix may underlie the capacity of tumor cells to colonize and survive in the bone microenvironment. Of particular importance, urokinase-type plasminogen activator (uPA) has been shown to correlate with human prostate cancer (PC) metastasis. The importance of this protease may be related to its ability to initiate a proteolytic cascade, leading to the activation of multiple proteases and growth factors. Previously, we showed that maspin, a serine protease inhibitor, specifically inhibits PC-associated uPA and PC cell invasion and motility in vitro. In this article, we showed that maspin-expressing transfectant cells derived from PC cell line DU145 were inhibited in in vitro extracellular matrix and collagen degradation assays. To test the effect of tumor-associated maspin on PC-induced bone matrix remodeling and tumor growth, we injected the maspin-transfected DU145 cells into human fetal bone fragments, which were previously implanted in immunodeficient mice. These studies showed that maspin expression decreased tumor growth, reduced osteolysis, and decreased angiogenesis. Furthermore, the maspin-expressing tumors contained significant fibrosis and collagen staining, and exhibited a more glandular organization. These data represent evidence that maspin inhibits PC-induced bone matrix remodeling and induces PC glandular redifferentiation. These results support our current working hypothesis that maspin exerts its tumor suppressive role, at least in part, by blocking the pericellular uPA system and suggest that maspin may offer an opportunity to improve therapeutic intervention of bone metastasis.A ndrogen deprivation therapy has been the mainstay of treatment of metastatic prostate cancer (PC) for Ͼ50 years. Usually, this therapy produces tremendous tumor shrinkage and significant clinical improvement. However, the duration of response is limited and disease always recurs. Cytotoxic chemotherapy is commonly added, although this approach offers little chance for meaningful, long-term survival. Thus, new approaches are needed. The skeleton is the major target organ of metastasis in patients with PC, and bone metastasis is associated with poor survival. Can bone-targeted therapy improve survival? In a recent clinical trial (1), a therapeutic, bone-seeking radioisotope was added to standard chemotherapy in patients showing an initial chemotherapeutic response. Survival was prolonged in the patients receiving the bone-seeking radioisotope compared with those receiving chemotherapy alone, suggesting that targeting skeletal metastases is a promising approach in PC treatment.Clinicians have traditionally classified bone metastases as either osteolytic or osteoblastic (2). However, tumor deposits in bone usually contain both bone formation and bone degradation (3-8). A ''vicious cycle'' is created whereby metastatic tumor stimulates bone turnover and bone turnover promotes local tumor growth. To date, various molecules have been implicated ...

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Activation of ProMMP‐9 by a Plasmin/MMP‐3 Cascade in a Tumor Cell Model: Regulation by Tissue Inhibitors of Metalloproteinases

Cited by 85 publications

References 37 publications

Caveolin-1 mediates the expression and localization of cathepsin B, pro-urokinase plasminogen activator and their cell-surface receptors in human colorectal carcinoma cells

Caveolin-1 mediates the expression and localization of cathepsin B, pro-urokinase plasminogen activator and their cell-surface receptors in human colorectal carcinoma cells

Single nucleotide polymorphisms in matrix metalloproteinase genes and lung cancer chemotherapy response and prognosis

Maspin expression inhibits osteolysis, tumor growth, and angiogenesis in a model of prostate cancer bone metastasis

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