References of "Maquoi, Erik"
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See detailModulation of fibrinolytic and gelatinolytic activity during adipose tissue development in a mouse model of nutritionally induced obesity
Lijnen, Roger; Maquoi, Erik ULg; Demeulemeester, Désiré et al

in Thrombosis and Haemostasis (2002), 88(2), 345-353

A nutritionally induced obesity model was used to investigate the modulation of fibrinolytic and gelatinolytic activity during the development of adipose tissue. Five week old male mice were fed a ... [more ▼]

A nutritionally induced obesity model was used to investigate the modulation of fibrinolytic and gelatinolytic activity during the development of adipose tissue. Five week old male mice were fed a standard fat diet (SFD, 13% kcal as fat) or a high fat diet (HFD, 42% kcal as fat) for up to 15 weeks. The HFD resulted in body weights of 31 +/- 0.9 g, 38 +/- 2.0 g and 47 +/- 1.9 g at 5, 10 and 15 weeks, respectively; corresponding values for mice on the SFD were 26 +/- 0.6 g, 31 +/- 0.9 g and 31 +/- 1.2 g (all p < 0.001). The weight of the isolated subcutaneous (s.c.) or gonadal (GON) fat after 15 weeks of HFD was 1,870 +/- 180 mg or 1,470 +/- 160 mg, as compared to 250 +/- 58 mg or 350 +/- 71 mg for the SFD (p < 0.001). The HFD induced marked time-dependent hyperglycemia and elevated levels of triglycerides and total cholesterol. The HFD diet also induced a marked hypertrophy of the adipocytes as compared to the SFD, e.g. diameter of 83 +/- 3.0 microns versus 52 +/- 4.2 microns for GON adipocytes at 15 weeks (p < 0.005). Plasma plasminogen activator inhibitor-1 (PAI-1) levels were higher in mice on the HFD as compared to the SFD; they were comparable in extracts of s.c. or GON adipose tissue, whereas at different time points tissue-type (t-PA) and urokinase-type (u-PA) plasminogen activator activity was somewhat lower in the adipose tissues of mice on HFD. Gelatinolytic activity (mainly MMP-2) was detected in s.c. but not in GON adipose tissue of mice on SFD, and decreased on the HFD. In situ zymography on cryosections did not reveal different fibrinolytic activities in s.c. or GON adipose tissues of the HFD as compared to the SFD groups, whereas significantly lower gelatinolytic and higher caseinolytic activities were detected in s.c. and GON tissues of mice on the HFD (p < or = 0.05). The fibrillar collagen content was lower in adipose tissue of mice on HFD. Thus, in this model time-dependent development of adipose tissue appears to be associated with modulation of proteolytic activity. [less ▲]

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See detailModulation of adipose tissue expression of murine matrix metalloproteinases and their tissue inhibitors with obesity
Maquoi, Erik ULg; Munaut, Carine ULg; Colige, Alain ULg et al

in Diabetes (2002), 51(4), 1093-1101

The potential role of the matrix metalloproteinase (MMP) system in the pathophysiology of the adipose tissue was investigated in a mouse model of nutritionally induced obesity. mRNA levels of 16 MMPs and ... [more ▼]

The potential role of the matrix metalloproteinase (MMP) system in the pathophysiology of the adipose tissue was investigated in a mouse model of nutritionally induced obesity. mRNA levels of 16 MMPs and 4 tissue inhibitors of MMPs (TIMPs) were measured by semiquantitative RT-PCR in adipose tissue isolated from mice maintained for 15 weeks on a standard or high-fat diet. In mice on standard diet, with the exception of MMP-8, all MMP and TIMP transcripts were detected in both gonadal and subcutaneous depots. In obese mice, the expression of MMP-3, -11, -12, -13, and -14 and TIMP-1 mRNAs was upregulated, whereas that of MMP-7, -9, -16, and -24 and TIMP-4 was downregulated. Most MMP and TIMP mRNAs were expressed at higher levels in stromal-vascular cells than in mature adipocytes. Analysis of adipose tissue by in situ fluorescent zymography revealed MMP-dependent proteolytic activities, demonstrating the presence of active MMPs in the intact tissue. In vitro conversion of adipogenic 3T3-F442A cells into mature adipocytes was associated with substantial modulations of MMP and TIMP expression. Moreover, this in vitro adipogenesis was reduced in the presence of a synthetic MMP inhibitor. Thus, the adipose tissue expresses a large array of MMPs and TIMPs, which modulate adipocyte differentiation. [less ▲]

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See detailMatrix metalloproteinase inhibition impairs adipose tissue development in mice
Lijnen, Roger; Maquoi, Erik ULg; Hansen, L. B. et al

in Arteriosclerosis, Thrombosis, and Vascular Biology (2002), 22(3), 374-379

The effect of galardin, a broad-spectrum matrix metalloproteinase (MMP) inhibitor, was studied in mice kept on a high fat diet (HFD). Five-week-old male wild-type mice were fed the HFD (42% fat) for up to ... [more ▼]

The effect of galardin, a broad-spectrum matrix metalloproteinase (MMP) inhibitor, was studied in mice kept on a high fat diet (HFD). Five-week-old male wild-type mice were fed the HFD (42% fat) for up to 12 weeks and were daily injected intraperitoneally with the inhibitor (100 mg/kg) or with vehicle. After 12 weeks of the HFD, the body weights of both groups were comparable, but the weight of the isolated subcutaneous (SC) or gonadal (GON) fat deposits was significantly lower in the inhibitor-treated group than in the control group (88 +/- 11 versus 251 +/- 66 mg, respectively, for SC fat [P<0.05]; 90 +/- 24 versus 217 +/- 30 mg, respectively, for GON fat [P<0.02]). The number of adipocytes was somewhat higher and the diameter was somewhat smaller (but not significantly) in adipose tissues of the inhibitor-treated group. Adipose tissue of the inhibitor-treated mice contained more collagen than did that of the vehicle-treated mice (Sirius red-stained area of 42 +/- 2.6% versus 22 +/- 4.4%, respectively, for SC fat [P<0.05]; 21 +/- 5.1% versus 4.7 +/- 0.92%, respectively, for GON fat [P<0.01]); a distinct collagen-rich cap was formed around the inhibitor-treated tissue. In situ zymography with casein- or gelatin-containing gels confirmed a reduced MMP activity in SC and GON adipose tissues of inhibitor-treated mice. Thus, in this model, growth and development of adipose tissue appears to be limited by the formation of a collagen-rich matrix cap around the inhibitor-treated tissue. These data suggest a functional role for MMPs in the development of adipose tissue. [less ▲]

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See detailExpression of membrane type 1 matrix metalloproteinase (MT1-MMP) in A2058 melanoma cells is associated with MMP-2 activation and increased tumor growth and vascularization
Sounni, Nor Eddine ULg; Baramova, Eugénia; Munaut, Carine ULg et al

in International Journal of Cancer = Journal International du Cancer (2002), 98(1), 23-28

Membrane-type metalloproteinase-1 (MT1-MMP) is a transmembrane metalloproteinase overexpressed in tumors, which plays a major role in the first step of pro-MMP-2 activation, leading to the generation of ... [more ▼]

Membrane-type metalloproteinase-1 (MT1-MMP) is a transmembrane metalloproteinase overexpressed in tumors, which plays a major role in the first step of pro-MMP-2 activation, leading to the generation of an intermediate 62 kDa species. The second step of MMP-2 activation that yields to the mature form is less understood and could involve an autocatalytic process and/or the activity of the plasminogen/plasmin system. Human melanoma A2058 cells, which express MMP-2 only in its pro-form, were used to determine the role of MT1-MMP during pericellular proteolysis and tumor progression. The induction of MT1-MMP overexpression by MT1-MMP cDNA transfection initiated the first step of MMP-2 activation. We provide evidence that a cooperation between the plasminogen/plasmin system and MT1-MMP endowed the cells with the ability to fully activate MMP-2 and with enhanced invasive properties in vitro. When injected subcutaneously in nude mice, MT1-MMP expressing clones induced rapid tumor growth and high tumor vascularization, while the control clones were poorly or not tumorigenic. Our data provide the first demonstration, in an experimental model, that MT1-MMP expression by tumor cells promotes tumor vascularization. [less ▲]

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See detailStimulation of matrix metalloproteinase-9 expression in human fibrosarcoma cells by synthetic matrix metalloproteinase inhibitors.
Maquoi, Erik ULg; Munaut, Carine ULg; Colige, Alain ULg et al

in Experimental Cell Research (2002), 275(1), 110-21

Enhanced expression and activation of matrix metalloproteinase-2 (MMP-2) and MMP-9 have been associated with tumor progression, invasion, and metastasis. The use of synthetic MMP inhibitors to block the ... [more ▼]

Enhanced expression and activation of matrix metalloproteinase-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 beta-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 Il-1beta and TNF-alpha 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. [less ▲]

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See detailAdipose tissue expression of gelatinases in mouse models of obesity.
Lijnen, roger; Maquoi, Erik ULg; Holvoet, P. et al

in Thrombosis and Haemostasis (2001), 85(6), 1111-1116

Following the observation by Brown et al. (Am J Physiol 1997; 272: C937-49) that primary rat adipocytes in culture secrete gelatinase A (MMP-2), we have evaluated gelatinase expression in adipose tissue ... [more ▼]

Following the observation by Brown et al. (Am J Physiol 1997; 272: C937-49) that primary rat adipocytes in culture secrete gelatinase A (MMP-2), we have evaluated gelatinase expression in adipose tissue with the use of mouse models of obesity. Wild-type mice were kept on a standard fat diet (SFD) or on a high fat diet (42% fat, HFD) and- genetically obese db/db mice were kept on SFD; gonadal and subcutaneous fat pads were removed and analysed ex vivo. These studies revealed that: 1) the HFD induced adipocyte hypertrophy; 2) after 32 weeks, significantly higher levels of 70 kDa (p <0.05) and 65 kDa proMMP-2 (p <0.01) were observed in extracts of gonadal fat pads of mice on HFD; 3) the contribution of active MMP-2 to the total level was comparable in SFD and HFD groups (20 to 30%); and 4) gelatinase B (MMP-9) was not consistently detected. These findings were confirmed by gelatin zymography and by mRNA determination using competitive RT-PCR. The presence of MMP-2 in the adipose tissue was confirmed immunologically and its localization in adipocytes revealed by immunogold electron microscopy. The potential functional role of MMP-2 in adipose tissue remains to be determined. [less ▲]

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See detailNew Functions of Stromal Proteases and Their Inhibitors in Tumor Progression
Noël, Agnès ULg; Albert, V.; Bajou, Khalid ULg et al

in Surgical Oncology Clinics of North America (2001), 10(2), 417-32

Acquisition of invasive metastatic potential through protease expression is a key event in tumor progression. In carcinomas, the production of metalloproteinases and serine proteinases is regulated by a ... [more ▼]

Acquisition of invasive metastatic potential through protease expression is a key event in tumor progression. In carcinomas, the production of metalloproteinases and serine proteinases is regulated by a cross talk between stromal cells and cancer cells. Paradoxically, high rather than low levels of their inhibitors predict poor survival of patients suffering from a variety of cancers. Recent observations suggest a much more complex role of these inhibitors in tumor progression than expected initially. [less ▲]

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See detailType Iv Collagen Induces Matrix Metalloproteinase 2 Activation in Ht1080 Fibrosarcoma Cells
Maquoi, Erik ULg; Frankenne, F.; Noël, Agnès ULg et al

in Experimental Cell Research (2000), 261(2), 348-59

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 ... [more ▼]

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. [less ▲]

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See detailMembrane Type 1 Matrix Metalloproteinase-Associated Degradation of Tissue Inhibitor of Metalloproteinase 2 in Human Tumor Cell Lines
Maquoi, Erik ULg; Frankenne, Francis ULg; Baramova, Eugénia et al

in Journal of Biological Chemistry (2000), 275(15), 11368-78

Tissue inhibitor of metalloproteinase 2 (TIMP-2) is required for the membrane type 1 matrix metalloproteinase (MT1-MMP)-dependent activation of pro-MMP-2 on the cell surface. MT1-MMP-bound TIMP-2 has been ... [more ▼]

Tissue inhibitor of metalloproteinase 2 (TIMP-2) is required for the membrane type 1 matrix metalloproteinase (MT1-MMP)-dependent activation of pro-MMP-2 on the cell surface. MT1-MMP-bound TIMP-2 has been shown to function as a receptor for secreted pro-MMP-2, resulting in the formation of a trimolecular complex. In the presence of uncomplexed active MT1-MMP, the prodomain of cell surface-associated MMP-2 is cleaved, and activated MMP-2 is released. However, the behavior of MT1-MMP-bound TIMP-2 during MMP-2 activation is currently unknown. In this study, (125)I-labeled recombinant TIMP-2 ((125)I-rTIMP-2) was used to investigate the fate of TIMP-2 during pro-MMP-2 activation by HT1080 and transfected A2058 cells. HT1080 and A2058 cells transfected with MT1-MMP cDNA (but not vector-transfected A2058 cells) were able to bind (125)I-rTIMP-2, to activate pro-MMP-2, and to process MT1-MMP into an inactive 43-kDa form. Under these conditions, (125)I-rTIMP-2 bound to the cell surface was rapidly internalized and degraded in intracellular organelles through a bafilomycin A(1)-sensitive mechanism, and (125)I-bearing low molecular mass fragment(s) were released in the culture medium. These different processes were inhibited by hydroxamic acid-based synthetic MMP inhibitors and rTIMP-2, but not by rTIMP-1 or cysteine, serine, or aspartic proteinase inhibitors. These results support the concept that the MT1-MMP-dependent internalization and degradation of TIMP-2 by some tumor cells might be involved in the regulation of pericellular proteolysis. [less ▲]

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See detailCell-Cell and Cell-Matrix Interactions During Breast Cancer Progression
Noël, Agnès ULg; Kebers, F.; Maquoi, Erik ULg et al

in Current Topics in Pathology. Ergebnisse der Pathologie (1999)

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See detailInhibition of Stromal Matrix Metalloproteases: Effects on Breast-Tumor Promotion by Fibroblasts
Noël, Agnès ULg; Hajitou, Amin; L'Hoir, Cécile et al

in International Journal of Cancer = Journal International du Cancer (1998), 76(2), 267-73

Co-injection of fibroblasts with human epithelial breast-tumor MCF7 cells in the presence of Matrigel enhances tumor growth in nude mice. While most of the matrix metalloproteinases (MMPs) have been shown ... [more ▼]

Co-injection of fibroblasts with human epithelial breast-tumor MCF7 cells in the presence of Matrigel enhances tumor growth in nude mice. While most of the matrix metalloproteinases (MMPs) have been shown to be produced by stromal cells, tumor cells such as MCF7 cells are unable to produce MMPs. We therefore, hypothesized that the tumor-promoting effect of fibroblasts could be related to their production of MMPs. In order to inhibit stromal proteases, over-production of TIMP-2 was induced in MCF7 cells by in vitro retroviral-mediated gene transfer. TIMP-2-producing MCF7 cells were then co-injected with fibroblasts into nude mice. Alternatively, we evaluated the effect of Batimastat, a synthetic inhibitor of MMPs, on the tumorigenicity of MCF7 cells co-inoculated with fibroblasts into nude mice. Both physiological (TIMP-2) and synthetic (Batimastat) inhibitors of MMPs were able to abolish the tumor-promoting effect of fibroblasts. On the contrary, they failed to modulate the tumorigenicity of MCF7 cells injected alone. Interestingly, Matrigel from which low-molecular-weight proteins or growth factors had been removed failed to favor the tumorigenicity of MCF7 cells inoculated with fibroblasts. These findings emphasize the importance of fibroblasts in cancer progression, and suggest that their role could be related at least in part to production of proteases which can induce the release of factors from the extracellular matrix. [less ▲]

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See detailInhibition of Matrix Metalloproteinase 2 Maturation and Ht1080 Invasiveness by a Synthetic Furin Inhibitor
Maquoi, Erik ULg; Noël, Agnès ULg; Frankenne, F. et al

in FEBS Letters (1998), 424(3), 262-6

The close correlation observed between matrix metalloproteinase 2 (MMP-2) activation and metastatic progression in various tumors suggests that MMP-2 is a 'master switch' triggering tumor spread. Recently ... [more ▼]

The close correlation observed between matrix metalloproteinase 2 (MMP-2) activation and metastatic progression in various tumors suggests that MMP-2 is a 'master switch' triggering tumor spread. Recently, membrane type 1 MMP (MT1-MMP) was identified as a potential physiological activator of MMP-2. Like all other MMPs, MT1-MMP possesses a pro-domain which must be removed for the enzyme to acquire its catalytic potential. The presence of a typical recognition motif (RXKR) for the furin-like convertases at the end of its pro-domain suggests a potential role for these proteinases in MT1-MMP processing. In order to evaluate the implication of furin in pro-MT1-MMP processing, we treated HT1080 cells with a synthetic furin inhibitor and monitored their ability to activate pro-MMP-2 as well as their invasive potential. Our results demonstrated that the furin inhibitor decreased pro-MT1-MMP processing as well as pro-MMP-2 activation and cell invasiveness. Therefore, our data bring further evidence that furin is a key factor in the maturation of MMPs associated with the invasive and metastatic potential of tumor cells. [less ▲]

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See detailExpression of Stromelysin-3 in the Human Placenta and Placental Bed
Maquoi, Erik ULg; Polette, M.; Nawrocki, B. et al

in Placenta (1997), 18(4), 277-85

Human placentation is mediated by fetal trophoblastic cells which penetrate into the decidualized uterine endometrium. Trophoblast invasion requires the precisely regulated secretion of specific ... [more ▼]

Human placentation is mediated by fetal trophoblastic cells which penetrate into the decidualized uterine endometrium. Trophoblast invasion requires the precisely regulated secretion of specific proteinases able to degrade the endometrial basement membranes and extracellular matrix. To document further the involvement of these proteinases during human placentation, we evaluated in vivo the expression of stromelysin-3, a member of the metalloproteinase family, during the first and third trimesters of pregnancy, by means of immunohistochemistry, in situ hybridization and Northern blot analysis. Human extravillous trophoblasts invading the maternal decidua produced stromelysin-3 during both, the first and third trimesters of pregnancy, but to a lesser extent during the latter. In floating villi, stromelysin-3 expression was restricted to the syncytiotrophoblasts that line intervillous vascular spaces. In conclusion, stromelysin-3 is expressed by differentiated, non-proliferative villous and extravillous trophoblastic cells in early and late placental beds and villi, and its pattern of expression evolves during pregnancy. Our observations suggest that stromelysin-3 could play a role in human placentation. [less ▲]

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See detailChanges in the Distribution Pattern of Galectin-1 and Galectin-3 in Human Placenta Correlates with the Differentiation Pathways of Trophoblasts
Maquoi, Erik ULg; van den Brule, F. A.; Castronovo, Vincenzo ULg et al

in Placenta (1997), 18(5-6, Jul-Aug), 433-9

Human placentation is a complex biological phenomenon that results from precisely regulated interactions between cells and the extracellular matrix. Galectin- 1 and galectin-3 belong to a newly defined ... [more ▼]

Human placentation is a complex biological phenomenon that results from precisely regulated interactions between cells and the extracellular matrix. Galectin- 1 and galectin-3 belong to a newly defined family of galactose-binding lectins that can bind several glycoconjugates such as the basement membrane glycoprotein laminin, and are involved in many biological events including cell adhesion. In this study, the expression of these two galectins in first and third trimester normal human placenta was examined using single and double immunohistochemical staining and specific antibodies for galectins and cytokeratins. Galectin-3 was detected in all trophoblastic lineages including villous cytotrophoblasts and extravillous trophoblasts (trophoblastic cell columns, infiltrating trophoblasts, endovascular trophoblasts and placental bed giant cells). On the contrary, galectin-1 distribution was restricted to endometrium. A reduction of galectin-3 expression was observed from the villous trophoblasts to the trophoblastic cell columns. This pattern correlated with the switch from a proliferative to a migratory phenotype. Galectin-1 and galectin-3 were both detected in maternal decidual cells. Our data demonstrate a specific pattern of galectin-1 and galectin-3 expression in trophoblastic tissue, and suggest these lectins could contribute to cell-cell and cell matrix interactions of trophoblast during placentation. [less ▲]

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See detailMatrix metalloproteinases in choriocarcinoma cell lines: a potential regulatory role of extracellular matrix components
Maquoi, Erik ULg; Noël, Agnès ULg; Foidart, Jean-Michel ULg

in Foidart, Jean-Michel; Aplin, J.; Kaufmann, P. (Eds.) et al Trophoblast Research. Early Pregnancy (1997)

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See detailEmerging Roles for Proteinases in Cancer
Noël, Agnès ULg; Gilles, Christine ULg; Bajou, Khalid ULg et al

in Invasion & Metastasis (1997), 17(5), 221-39

Metalloproteinases and serine proteinases have been associated with tumor invasion and formation of metastasis which represent the major obstacles to cancer cure. The contribution of proteinases in these ... [more ▼]

Metalloproteinases and serine proteinases have been associated with tumor invasion and formation of metastasis which represent the major obstacles to cancer cure. The contribution of proteinases in these processes was initially thought to be the destruction of extracellular matrices. However, recent evidence suggests that they mainly affect tumor growth rather than invasion. Proteinases can indeed generate active matrix protein fragments, influence the release, the activation and the bioavailability of growth factors, and consequently modulate tumor cell growth, apoptosis and angiogenesis. Additionally, proteinases, their receptors and/or inhibitors can be directly involved in cell migration and in the processing or shedding of cell surface proteins. Further elucidation of the functions of proteinases is essential for the development of novel anticancer strategies. [less ▲]

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See detailLa prééclampsie est la conséquence d'un déficit de placentation: de la biologie aux considérations cliniques
Maquoi, Erik ULg; Schaaps, Jean-Pierre ULg; Jacobs, J. L. et al

in Revue Médicale de Liège (1997), 52(7), 478-84

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See detailMembrane-type matrix metalloproteinase-1 expression at the site of human placentation
Nawrocki, B.; Polette, M. E.; Marchand, V. et al

in Placenta (1996), 17(8), 565-72

Human trophoblast implantation is a highly regulated process of invasion that requires action of proteolytic enzymes to degrade extracellular matrix components of the endometrium. Among these enzymes ... [more ▼]

Human trophoblast implantation is a highly regulated process of invasion that requires action of proteolytic enzymes to degrade extracellular matrix components of the endometrium. Among these enzymes, matrix metalloproteinases (MMPs) seem to be particularly important in this degradative process. We previously showed that gelatinase A is extensively expressed in vivo in the human placenta. A new MMP, MT-MMP-1 (membrane-type matrix metalloproteinase-1), which is thought to activate progelatinase A, has recently been described. In this study, we examined the expression of MT-MMP-1, by immunohistochemistry and in situ hybridization, in human placental bed biopsies taken during the first trimester of gestation. Human first trimester intermediate trophoblasts synthesized MT-MMP-1 mRNAs and the protein. The MT-MMP-1 pattern of distribution in placental beds was similar to that of gelatinase A, suggesting a pivotal role for MT-MMP-1 in placentation, perhaps by activating progelatinase A. [less ▲]

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See detailStromelysin-3 expression promotes tumor take in nude mice
Noël, Agnès ULg; Lefebvre, O.; Maquoi, Erik ULg et al

in Journal of Clinical Investigation (1996), 97

Stromelysin-3 (ST3) is a matrix metalloproteinase expressed in human carcinomas in ways suggesting that it may play a role in tumor progression. To test this possibility, we have performed gene transfer ... [more ▼]

Stromelysin-3 (ST3) is a matrix metalloproteinase expressed in human carcinomas in ways suggesting that it may play a role in tumor progression. To test this possibility, we have performed gene transfer experiments using both anti-sense and sense ST3 expression vectors, and malignant cells either expressing (NIH 3T3 fibroblasts) or not (MCF7 epithelial cells) endogenous ST3. We have compared the ability of parental and transfected cells to cause subcutaneous tumor development in nude mice. 3T3 cells expressing anti-sense ST3 RNA showed reduced tumorigenicity, and MCF7 cells expressing mouse or human ST3 were associated with reduced tumor-free period leading to a significant increased tumor incidence(P<10(-4)). However, once established, the ST3 expressing tumors did not grow faster than those obtained with the parental MCF7 cell line. In addition, tumors obtained after sub-cutaneous injection of ST3-expressing or nonexpressing cells did not exhibit obvious histological differences, and careful examination did not reveal any local invasive tissue areas nor systemic metastases. These in vivo observations were in agreement with those obtained in vitro showing that ST3 expression did not modify proliferative nor invasive properties of transfected cells. Altogether, these results indicate that ST3 expression promotes tumor take in nude mice, presumably by favoring cancer cell survival in a tissue environment initially not permissive for tumor growth. These findings represent the first experimental evidence showing that ST3 can modulate cancer progression. [less ▲]

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