Involvement of PA/plasmin system in the processing of pro‐MMP‐9 and in the second step of pro‐MMP‐2 activation

Baramova, Eugenia N.; Bajou, Khalid; Remacle, Albert G.; L'Hoir, Cécile; Krell, Hans-Willi; Weidle, Ulrich H.; Noël, Agnès; Foidart, Jean‐Michel

doi:10.1016/s0014-5793(97)00175-0

Cited by 245 publications

(192 citation statements)

References 31 publications

(27 reference statements)

Supporting

Mentioning

166

Contrasting

Unclassified

Order By: Relevance

“…However, MMP-9 could be activated in vivo by other proteinases such as serine proteinases. In this respect, it has been previously demonstrated that, in HT1080 cells, the conversion of plasminogen to plasmin through cell surface-bound urokinase-type plasminogen activator was able to activate endogenously secreted MMP-9 [29]. Here, we report that the addition of plasminogen to HT1080 cultures induced the conversion of 92-kDa pro-MMP-9 to activated 85-kDa form in a concentration-dependent manner (Fig.…”

Section: Gi129471 Does Not Prevent the Plasminogen-dependent Pro-mmp-supporting

confidence: 60%

“…The activation of MMP-9 has been demonstrated to be essentially mediated by plasmin [29,49]. In this study, we used HT1080 cells, which synthesize urokinase-type plasminogen activator (uPA) and its cell surface receptor (uPAR) but not plasminogen [29,49].…”

Section: Discussionmentioning

confidence: 99%

“…Recombinant human TIMP-1 (rTIMP-1) was a gift of Prof. G. Murphy (School of Biological Sciences, University of East Anglia, Norwich, UK). Recombinant human TIMP-2 (rTIMP-2) was produced from transformed CHO cells conditioned medium as previously described [29]. Human plasminogen was purified by affinity chromatography on lysineSepharose [30].…”

Section: Cell Culture and Reagentsmentioning

confidence: 99%

See 2 more Smart Citations

Stimulation of Matrix Metalloproteinase-9 Expression in Human Fibrosarcoma Cells by Synthetic Matrix Metalloproteinase Inhibitors

Maquoi

Munaut

Colige

et al. 2002

Experimental Cell Research

View full text Add to dashboard Cite

Enhanced expression and activation of matrix met-alloproteinase-2 (MMP-2) and MMP-9 have been associated with tumor progression, invasion, and metastasis. The use of synthetic MMP inhibitors to block the proteolytic activity of these enzymes recently emerged as a potential therapeutic tool to treat cancer. In this study, we report that GI129471, a synthetic broad-spectrum MMP inhibitor, efficiently reduced the in vitro invasiveness of HT1080 cells through type IV collagen, a major component of basement membranes. This reduced invasion was paralleled by a complete inhibition of pro-MMP-2 activation; however, GI129471 strongly increased the amount of secreted pro-MMP-9, which could be subsequently activated through a plasminogen-dependent mechanism. Quantitative RT-PCR and northern blot analysis revealed that GI129471 specifically increased the MMP-9 mRNA steady-state level. Moreover, transient transfection of HT1080 cells with β-galactosidase reporter vectors containing different lengths of the 5'-flanking region of the MMP-9 gene revealed an upregulation of the transcriptional activity of the corresponding promoter. Well-known modulators of MMP-9 expression such as 11-1β and TNF-α were not involved in this upregulation. These findings emphasize the complexity of the regulation of MMP expression and the requirement for a detailed characterization of the potential adverse side effects associated with the use of broad-Spectrum MMPIs.

show abstract

Section: Gi129471 Does Not Prevent the Plasminogen-dependent Pro-mmp-supporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Cell Culture and Reagentsmentioning

confidence: 99%

See 1 more Smart Citation

Stimulation of Matrix Metalloproteinase-9 Expression in Human Fibrosarcoma Cells by Synthetic Matrix Metalloproteinase Inhibitors

Maquoi

Munaut

Colige

et al. 2002

Experimental Cell Research

View full text Add to dashboard Cite

show abstract

“…IB, lane 1). This latter band represents an intermediate activated form of MMP-2 which has been previously shown to result from a MT1-MMP-depen-dent proteolytic processing of pro-MMP-2 [20,31,32]. After 48 h, the amount of 62-kDa MMP-2 increased in both conditioned medium and cell extract [accounting for 10 and 35% of total MMP-2 activity, respectively (Figs.…”

Section: Ecm Components Modulate Pro-mmp-2 Activationmentioning

confidence: 78%

Type IV Collagen Induces Matrix Metalloproteinase 2 Activation in HT1080 Fibrosarcoma Cells

Maquoi

Frankenne

Noël

et al. 2000

Experimental Cell Research

View full text Add to dashboard Cite

Matrix metalloproteinase 2 (MMP-2) activation has been described as a "master switch" which triggers tumor spread and metastatic progression. We show here that type IV collagen, a major component of basement membranes, promotes MMP-2 activation by HT1080 cells. When plated on plastic, HT1080 cells constitutively processed the 66-kDa pro-MMP-2 into a 62-kDa intermediate activated form, most probably through a membrane type (MT) 1 MMP-dependent mechanism. In the presence of type IV collagen, part of this intermediate form was further processed to fully activated 59-kDa MMP-2. This activation was prevented by tissue inhibitor of MMP (TIMP)-2 and a broad-spectrum hydroxamic acid-based synthetic MMP inhibitor (GI129471). Type IV collagen-mediated pro-MMP-2 activation did not involve either a transcriptional modulation of MMP-2, MT1-MMP, or TIMP-2 expression nor any alteration of MT1-MMP protein synthesis or processing. An inverse relationship between MMP-2 activation and the concentration of secreted TIMP-2 was observed. This is consistent with our previous report that TIMP-2 degradation is probably linked to the MT1-MMP-dependent MMP-2 activation mechanism. Because invasive tumor cells must breach basement membranes at different steps of the metastatic dissemination, the ability of HT1080 cells to activate pro-MMP-2 in the presence of type IV collagen might represent a key regulatory mechanism for the acquisition of an invasive potential.

show abstract

“…RA-activated retinoic acid receptors directly bind to the retinoic acid responsive element on the tPA gene promoter, and induce the transcriptional activation of tPA gene (Bulen et al, 1997). Plasminogen activators (uPA and tPA), and plasmin, which was proteolytically produced by the plasminogen activators, can activate the latent TGF-β and its family members (Imai et al, 1997), HGF (Mars et al, 1993), and proMMPs (Baramova et al, 1997). Thus, RAs enhance the migration, invasion and differentiation of the cells, and may act as a morphogen during the embryogenesis and the development.…”

Section: Discussionmentioning

confidence: 99%

Low-dose retinoic acid enhances in vitro invasiveness of human oral squamous-cell-carcinoma cell lines

et al. 2001

View full text Add to dashboard Cite

Summary Retinoids inhibit the proliferation of several types of tumour cells, and are used for patients with several malignant tumours. In this study, we examined the effect of retinoic acids (RAs) on the invasive potentials of the oral squamous cell carcinoma (SCC) cells, BHY and HNt. BHY cells expressed all of retinoid nuclear receptors (RARα, β, γ, and RXRα) and cytoplasmic retinoic acid binding proteins (CRABP1 and CRABP2). HNt cells lacked the expression of RARβ, but expressed other nuclear receptors and CRABPs. All-trans retinoic acid (ATRA) and 13-cis retinoic acid (13-cisRA) (10 -6 and 10 -7 M) inhibited the growth of the cells, but low-dose ATRA and 13-cisRA (10 -8 M) marginally affected the growth of the cells. Surprisingly, low-dose RAs enhanced the activity of tissue-type plasminogen activator (tPA), and activated pro-matrix metalloproteinases (proMMP2 and proMMP9). Activation of proMMP2 and proMMP9 was inhibited by aprotinin, a serineproteinase, tPA inhibitor. MATERIALS AND METHODS Cells and cell cultureBHY and HNt (Kawamata et al, 1997) cells were derived from human oral SCC tumours from patients. HT1080 cells are a human fibrosarcoma cell line purchased from Dai-Nippon Seiyaku, Osaka, Japan. All of the cells were maintained in DMEM (Life Technologies, Inc, Gaithersburg, MD) supplemented with 10% FCS (Bio-Whittaker, Walkersville, MD), 100 µg ml -1 streptomycin, and 100 U ml -1 penicillin, 0.25 µg ml -1 Amphotericin B (Life Technologies, Inc.) in a humidified atmosphere of 95% air and 5% CO 2 at 37˚C. MTT assayWe examined the effect of ATRA (Sigma, St. Louis, MO) and 13-cisRA (Sigma) on the growth of the cells by an assay in which MTT (Sigma) was used. Cells were seeded on a 96-well plate (Falcon; Becton Dickinson Labware, Lincoln Park, NJ) at 5 × 10 3 cells per well in DMEM containing 10% FCS. After 24 h, cells were washed twice with DMEM without FCS and cultured in DMEM without FCS in the presence or absence of ATRA (10 -6 , 10 -7 and 10 -8 M) or 13-cisRA (10 -6 , 10 -7 and 10 -8 M). After 3 days, the number of cells was quantitated by MTT assay (Carmichael et al, 1987). Gelatinase zymography and reverse gelatinase zymographyCells were grown to confluence in 60 mm dishes (Falcon) in the serum-supplemented medium, washed twice with serum-free DMEM, and cultured in 3 ml of serum-free DMEM in the presence or absence of ATRA (10 -8 M) or 13-cisRA (10 -8 M) for an additional 48 h. The medium was collected, clarified by centrifugation at 1800 g, and concentrated down to 0.1 ml approximately 30-fold by Centricon 10 (cut-off, Mr 10 000; Millipore Corp, Bedford, MA). We have already confirmed that the process of the protein concentration did not activate the progelatinases in the samples (Kawamata et al, 1997). The protein concentration of the samples are determined by Bio-Rad protein assay (Bio-Rad, Hercules, CA). The gels for zymorgraphy were composed of gelatin (0.1%; Sigma) and polyacrylamide (10%), and for reverse zymography, of gelatin (0.1%), polyacrylamide (12.5%) and concentrated conditioned medi...

show abstract

Involvement of PA/plasmin system in the processing of pro‐MMP‐9 and in the second step of pro‐MMP‐2 activation

Cited by 245 publications

References 31 publications

Stimulation of Matrix Metalloproteinase-9 Expression in Human Fibrosarcoma Cells by Synthetic Matrix Metalloproteinase Inhibitors

Stimulation of Matrix Metalloproteinase-9 Expression in Human Fibrosarcoma Cells by Synthetic Matrix Metalloproteinase Inhibitors

Type IV Collagen Induces Matrix Metalloproteinase 2 Activation in HT1080 Fibrosarcoma Cells

Low-dose retinoic acid enhances in vitro invasiveness of human oral squamous-cell-carcinoma cell lines

Contact Info

Product

Resources

About