RGDS and DGEA-induced [Ca2+]i signalling in human dermal fibroblasts.
Mineur, Pierre ; ; Lambert, Charles et al
in Biochimica et Biophysica Acta (2005), 1746(1), 28-37
A pulse of short peptides, RGDS and DGEA in the millimolar range, immediately elicits in normal human fibroblasts a transient increase of intracellular Ca2+ ([Ca2+]i). In the present study, we show that ... [more ▼]
A pulse of short peptides, RGDS and DGEA in the millimolar range, immediately elicits in normal human fibroblasts a transient increase of intracellular Ca2+ ([Ca2+]i). In the present study, we show that this [Ca2+]i occurs in an increasing number of cells as a function of peptides concentration. It is specific of each peptide and inhibited at saturating concentration of the peptide in the culture medium. The [Ca2+]i transient depends on signalling pathways slightly different for DGEA and RGDS involving tyrosine kinase(s) and phosphatase(s), phospholipase C, production of inositol-trisphosphate and release of Ca2+ from the cellular stores. GFOGER, the classical collagen binding peptide of alpha1- alpha2- and alpha11-beta1 integrins, in triple helical or denatured form, does not produce any Ca2+ signal. The [Ca2+]i signalling induced by RGDS and DGEA is inhibited by antibodies against beta1 integrin subunit while that mediated by RGDS is also inhibited by antibodies against the alpha3 integrin. Delay in the acquisition of responsiveness is observed during cell adhesion and spreading on a coat of fibronectin for RGDS or collagen for DGEA or on a coat of the specific integrin-inhibiting antibodies but not by seeding cells on GFOGER or laminin-5. This delay is suppressed specifically by collagenase acting on the collagen coat or trypsin on the fibronectin coat. Our results suggest that free integrins and associated focal complexes generate a Ca2+ signal upon recognition of DGEA and RGDS by different cellular pathways. [less ▲]Detailed reference viewed: 20 (2 ULg)
Cell survival and preservation of siRNA-mediated protein knock-down upon serum-free cryopreservation (-80 degrees C).
Lambert, Charles ; Deroanne, Christophe ; et al
in Gravitational and Space Biology Bulletin (2005), 18(2), 103-4Detailed reference viewed: 8 (1 ULg)
Murine bone marrow stromal cells sustain in vivo the survival of hematopoietic stem cells and the granulopoietic differentiation of more mature progenitors.
; Humblet, Chantal ; Belaid, Zakia et al
in Stem Cells (2005), 23(10), 1626-33
The study of the human hematopoietic system would be facilitated by availability of a relevant animal model. Because the medullar microenvironment is made of different types of cells, interactions between ... [more ▼]
The study of the human hematopoietic system would be facilitated by availability of a relevant animal model. Because the medullar microenvironment is made of different types of cells, interactions between hematopoietic cells and stromal cells are difficult to analyze in detail. As an approach for establishing an in vivo model to dissect these interactions, we grafted murine bone marrow fibroblastic cells (MS-5 cell line) with hematopoietic cells into the kidney capsule of syngenic mice. To identify the origin of cells present in the graft, we used green fluorescent protein-stable transfected MS-5 cells for the transplantation. To analyze the evolution of stromal cells and identify hematopoietic cells able to develop in these conditions, we performed morphology, histochemistry, and immunohistology on tissue sections at different times after transplantation. When injected alone, MS-5 cells differentiate into adipocytes. When injected with a bone marrow suspension or with isolated CD45+ cells (leukocytes), the stromal cells keep their fibroblastic morphology and their alkaline phosphatase expression and sustain granulopoiesis. When injected with hematopoietic stem cells called c-kit+ Sca-1+ Lin- suspension, clusters of hematopoietic cells are also observed: They do not present any granulopoietic activity and do not belong to B or T population nor to erythroid lineage. They are quiescent, induce bone marrow recovery and survival of lethally irradiated recipients, are able to form macroscopic colonies in the spleen, and are able to form very few colonies in vitro, suggesting that they are hematopoietic stem cells. In conclusion, our results show that reticular fibroblastic stromal cells MS-5 sustain the survival of stem cells and are not able to induce their differentiation. However, they can control differentiation, proliferation, and/or survival of hematopoietic cells engaged in myeloid lineage. [less ▲]Detailed reference viewed: 22 (1 ULg)
Gradient of proteolytic enzymes, their inhibitors and matrix proteins expression in a ruptured abdominal aortic aneurysm
; Colige, Alain ; Lambert, Charles et al
in European Journal of Clinical Investigation (2004), 34(7), 513-514Detailed reference viewed: 29 (4 ULg)
Changes in matrix gene and protein expressions after single or repeated exposure to one minimal erythemal dose of solar-simulated radiation in human skin in vivo
; Colige, Alain ; Deroanne, Christophe et al
in Photochemistry and Photobiology (2004), 79(3), 265-271
Damage to the skin extracellular matrix (ECM) is the hallmark of long-term exposure to solar UV radiation. The aim of our study was to investigate the changes induced in unexposed human skin in vivo after ... [more ▼]
Damage to the skin extracellular matrix (ECM) is the hallmark of long-term exposure to solar UV radiation. The aim of our study was to investigate the changes induced in unexposed human skin in vivo after single or repeated (five times a week for 6 weeks) exposure to I minimal erythemal dose (MED) of UV solar-simulated radiation. Morphological and biochemical analyses were used to evaluate the structural ECM components and the balance between the degrading enzymes and their physiologic inhibitors. A three-fold increase in matrix metalloproteinase 2 messenger RNA (mRNA) (P < 0.02, unexposed versus exposed) was observed after both single and repeated exposures. Fibrillin 1 mRNA level was increased by chronic exposure (P < 0.02) and unaltered by a single MED. On the contrary, a single MED significantly enhanced mRNA levels of interleukin-la (IL-1alpha), IL-1beta (P < 0.02) and plasminogen activator inhibitor-1 (P < 0.05). Immunohistochemistry demonstrated a significant decrease in Type-I procollagen localized just below the dermal-epidermal junction in both types of exposed sites. At the same location, the immunodetected tenascin was significantly enhanced, whereas a slight increase in Type-III procollagen deposits was also observed in chronically exposed areas. Although we were unable to observe any change in elastic fibers in chronically exposed buttock skin, a significant increase in lysozyme and alpha-1 antitrypsin deposits on these fibers was observed. These results demonstrate the existence of a differential regulation, after chronic exposure compared with an acute one, of some ECM components and inflammatory mediators. [less ▲]Detailed reference viewed: 10 (1 ULg)
Design and evaluation of new hydrogels for biomaterial purposes
Grandfils, Christian ; ; et al
Conference (2003, October 23)Detailed reference viewed: 3 (1 ULg)
Design and evaluation of new reinforced hydrogel membranes for biomaterial purposes
; Grandfils, Christian ; et al
Poster (2003, October 23)Detailed reference viewed: 6 (1 ULg)
TIMP-2 and PAI-1 mRNA levels are lower in aneurysmal as compared to athero-occlusive abdominal aortas.
; Colige, Alain ; Lambert, Charles et al
in Cardiovascular Research (2003), 60(1), 205-13
OBJECTIVE: Significant alterations of the vascular wall occurs in abdominal aortic aneurysm (AAA) and atherosclerotic occlusive disease (AOD) that ultimately may lead to either vascular rupture or ... [more ▼]
OBJECTIVE: Significant alterations of the vascular wall occurs in abdominal aortic aneurysm (AAA) and atherosclerotic occlusive disease (AOD) that ultimately may lead to either vascular rupture or obstruction. These modifications have been ascribed to one or a group of proteases, their inhibitors or to the matrix macromolecules involved in the repair process without considering the extent of the observed variations. METHODS: The mRNA steady-state level of a large spectrum of proteolytic enzymes (matrix metalloproteinases: MMP-1, -2, -3, -8, -9, -11, -12, -13, -14; urokinase plasminogen activator: u-PA), their physiological inhibitors (tissue inhibitors of MMPs: TIMP-1, -2, -3; plasminogen activator inhibitor: PAI-1) and that of structural matrix proteins (collagens type I and III, decorin, elastin, fibrillins 1 and 2) was determined by RT-PCR made quantitative by using a synthetic RNA as internal standard in each reaction mixture. The profile of expression was evaluated in AAA (n=7) and AOD (n=5) and compared to non-diseased abdominal (CAA, n=7) and thoracic aorta (CTA, n=5). RESULTS: The MMPs -8, -9, -12 and -13 mostly associated with inflammatory cells were not or barely detected in CAA and CTA while they were largely and similarly expressed in AAA and AOD. Expression of protease inhibitors or structural proteins were only slightly increased in both pathological conditions with the exception of elastin which was reduced. The main significant difference between AAA and AOD was a lower expression of TIMP-2 and PAI-1 in the aneurysmal lesions. CONCLUSIONS: The remodeling of the aortic wall in AAA and AOD involves gene activation of a large and similar spectrum of proteolytic enzymes while the expression of two physiological inhibitors, TIMP-2 and PAI-1, is significantly lower in AAA compared to AOD. The repair process in the aneurysmal disease seems similar to that of the occlusive disease. [less ▲]Detailed reference viewed: 47 (7 ULg)
Stimulation of matrix metalloproteinase-9 expression in human fibrosarcoma cells by synthetic matrix metalloproteinase inhibitors.
Maquoi, Erik ; Munaut, Carine ; Colige, Alain 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 ▲]Detailed reference viewed: 37 (11 ULg)
Cloning and characterization of ADAMTS-14, a novel ADAMTS displaying high homology with ADAMTS-2 and ADAMTS-3.
Colige, Alain ; ; Thiry, Marc et al
in Journal of Biological Chemistry (2002), 277(8), 5756-66
The processing of amino- and carboxyl-propeptides of fibrillar collagens is required to generate collagen monomers that correctly assemble into fibrils. Mutations in the ADAMTS2 gene, the ... [more ▼]
The processing of amino- and carboxyl-propeptides of fibrillar collagens is required to generate collagen monomers that correctly assemble into fibrils. Mutations in the ADAMTS2 gene, the aminopropeptidase of procollagen I and II, result in the accumulation of non-fully processed type I procollagen, causing human Ehlers-Danlos syndrome type VIIC and animal dermatosparaxis. In this study, we show that the aminopropeptide of type I procollagen can be cleaved in vivo in absence of ADAMTS-2 activity and that this processing is performed at the cleavage site for ADAMTS-2. In an attempt to identify the enzyme responsible for this alternative aminoprocollagen peptidase activity, we have cloned the cDNA and determined the primary structure of human and mouse ADAMTS-14, a novel ADAMTS displaying striking homologies with ADAMTS-2 and -3. The structure of the human gene, which maps to 10q21.3, and the mechanisms of generation of the various transcripts are described. The existence of two sites of initiation of transcription, in two different promoter contexts, suggests that transcripts resulting from these two sites can be differently regulated. The tissue distribution of ADAMTS-14, the regulation of the gene expression by various cytokines and the activity of the recombinant enzyme are evaluated. The potential function of ADAMTS-14 as a physiological aminoprocollagen peptidase in vivo is discussed. [less ▲]Detailed reference viewed: 8 (3 ULg)
Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in the human dermis.
Nusgens, Betty ; ; et al
in Journal of Investigative Dermatology (2001), 116(6), 853-9
Ascorbic acid (vitamin C) is a cofactor required for the function of several hydroxylases and monooxygenases. It is not synthesized in humans and some other animal species and has to be provided by diet ... [more ▼]
Ascorbic acid (vitamin C) is a cofactor required for the function of several hydroxylases and monooxygenases. It is not synthesized in humans and some other animal species and has to be provided by diet or pharmacologic means. Its absence is responsible for scurvy, a condition related in its initial phases to a defective synthesis of collagen by the reduced function of prolylhydroxylase and production of collagen polypeptides lacking hydroxyproline, therefore, they are unable to assemble into stable triple-helical collagen molecules. In fibroblast cultures, vitamin C also stimulates collagen production by increasing the steady-state level of mRNA of collagen types I and III through enhanced transcription and prolonged half-life of the transcripts. The aim of the experimental work has been to evaluate the effect on dermal cells of a preparation of vitamin C topically applied on one side vs placebo on the other side of the dorsal face of the upper forearm of postmenopausal women. Biopsies were collected on both sides and the level of mRNA measured by non competitive reverse transcription-polymerase chain reaction made quantitative by the simultaneous transcription and amplification of synthetic RNA used as internal standards. The mRNA of collagen type I and type III were increased to a similar extent by vitamin C and that of three post-translational enzymes, the carboxy- and amino-procollagen proteinases and lysyloxidase similarly increased. The mRNA of decorin was also stimulated, but elastin, and fibrillin 1 and 2 were not modified by the vitamin. The expression of matrix metalloproteinases 1, 2, and 9 was not significantly changed, but an increased level of tissue inhibitor of matrix metalloproteinase 1 mRNA was observed without modification of tissue inhibitor of matrix metalloproteinase 2 mRNA. The stimulating activity of topical vitamin C was most conspicuous in the women with the lowest dietary intake of the vitamin and unrelated to the level of actinic damage. The results indicate that the functional activity of the dermal cells is not maximal in postmenopausal women and can be increased. [less ▲]Detailed reference viewed: 128 (10 ULg)
Coordinated regulation of procollagens I and III and their post-translational enzymes by dissipation of mechanical tension in human dermal fibroblasts.
Lambert, Charles ; Colige, Alain ; et al
in European Journal of Cell Biology (2001), 80(7), 479-85
Mechanical tension governs fibroblast proliferation and survival and the homeostasis of the extracellular matrix to adapt its resistance to the mechanical requirements of the organs. To consolidate this ... [more ▼]
Mechanical tension governs fibroblast proliferation and survival and the homeostasis of the extracellular matrix to adapt its resistance to the mechanical requirements of the organs. To consolidate this view, we analysed the effect of tension release on the expression of molecules involved in the architecture and stabilisation of the collagen fibres, namely the procollagens type I and III, the amino- and carboxy-procollagen peptidases (N-pCP and C-pCP) and lysyl oxidase. Cells were cultured in conditions of high mechanical stress in monolayer on a collagen coat and under reduced tension by disruption of the cytoskeleton upon treatment with cytochalasin D in monolayer on a collagen coat or by integrin-mediated stress relaxation in a freely retracting collagen gel. The mRNAs were measured by quantitative RT-PCR monitored by simultaneous reverse-transcription and amplification of an original internal standard. Tension relaxation resulted in a decreased expression of the procollagens type I and III, of the two expressed forms of C-pCP, of the two forms of N-pCP and of lysyl oxidase. Type III collagen, known to control diameter of the fibres, was less down-regulated than type I collagen. Interestingly, the expression of the two alternatively spliced forms of the N-pCP was dissimilarly regulated. These data suggest that mechanical tension may modulate the stiffness of the extracellular matrix by controlling not only the level of expression of its fibrillar constituents but also that of the enzymes participating in their extracellular processing and mechanical stabilisation. [less ▲]Detailed reference viewed: 7 (0 ULg)
Microgravity stimulates the expression of interleukin-6 and matrix metalloproteinase-1 in human dermal fibroblasts
Lambert, Charles ; ; Colige, Alain et al
in Microgravity (2001)Detailed reference viewed: 9 (3 ULg)
Distinct pathways in the over-expression of matrix metalloproteinases in human fibroblasts by relaxation of mechanical tension.
Lambert, Charles ; Colige, Alain ; Munaut, Carine et al
in Matrix Biology (2001), 20(7), 397-408
The aim of the work was to analyze, on a comparative basis, the signaling pathways operating in the regulation of a panel of matrix metalloproteinases (MMP) expressed by human dermal fibroblasts submitted ... [more ▼]
The aim of the work was to analyze, on a comparative basis, the signaling pathways operating in the regulation of a panel of matrix metalloproteinases (MMP) expressed by human dermal fibroblasts submitted to mechanical stress relaxation by cytochalasin D (CD) and in a retracting collagen gel (RCG). The mRNA steady-state level of MMPs was measured by a quantitative RT-PCR procedure using a synthetic RNA as internal standard. In monolayer, most MMPs were barely detected, except MMP-2. Disruption of the actin stress fibers by CD induced a moderate increase of MMP-2 mRNA and a much larger stimulation of MMP-3, -9, -13 and -14 mRNAs. In RCG, a significant up-regulation of these MMPs was also observed although to a lower extent than in CD-treated monolayers. Among the investigated MMPs, the MMP-8 and -11 were not reproducibly detected. MMP-2 was processed to its active form both by CD and in RCG. The CD-induced up-regulation of gene expression was largely repressed by blocking protein synthesis by cycloheximide for all the MMPs, by inhibiting the tyrosine-kinases of the src family by herbimycin A for all MMPs, except MMP-2, and by inhibiting the TPA-inducible PKC isoforms by bisindoyl maleimide for all MMPs, except MMP-14. The up-regulation induced by stress relaxation in RCG was protein synthesis-dependent for MMP-2 and MMP-13, tyrosine kinases-dependent for MMP-3 and MMP-13, as previously described for MMP-1. Inhibiting TPA-inducible PKC did not affect any MMP in RCG except MMP-13, which was strongly induced. The processing of MMP-2 was tyrosine kinases-dependent but PKC-independent. Inhibitors of the ERK1,2 and p38 MAP kinases pathways diversely affected the MMPs expression. Inhibiting the Rho-kinase activity by Y-27632 was inactive. These results point to the potent regulation operated by the status of the cytoskeleton on the cell phenotype, and to distinct regulatory pathways involved in the control of different MMPs expression. [less ▲]Detailed reference viewed: 23 (2 ULg)
Paradoxical Stimulation of Matrix Metalloproteinase-9 Expression in Ht1080 Cells by a Broad-Spectrum Hydroxamate-Based Matrix Metalloproteinase Inhibitor
Maquoi, Erik ; Munaut, Carine ; Colige, Alain et al
in Annals of the New York Academy of Sciences (1999), 878Detailed reference viewed: 22 (4 ULg)
Modulation of Collagen and Fibronectin Synthesis in Fibroblasts by Normal and Malignant Cells
Noël, Agnès ; Munaut, Carine ; et al
in Journal of Cellular Biochemistry (1992), 48(2), 150-61
The influence of various normal and malignant human cells on the level of collagen synthesis by human fibroblasts was tested in coculture. As revealed by immunoperoxidase staining, in cocultures with ... [more ▼]
The influence of various normal and malignant human cells on the level of collagen synthesis by human fibroblasts was tested in coculture. As revealed by immunoperoxidase staining, in cocultures with breast adenocarcinoma cells (MCF7, SA52, T47D) fibroblasts synthesized collagen while tumor cells did not. Fibroblasts displayed increased collagen production without change in the overall protein synthesis. Several other types of cells derived from normal human tissues (keratinocytes, normal mammary cells) or from fibrosarcoma, melanoma, cervical carcinoma, choriocarcinoma, or other breast adenocarcinoma (SW613, MDA, BT20) did not affect collagen synthesis of fibroblasts. Although to a lesser extent, this stimulating effect was reproduced by using the conditioned medium (CM) of the active cells but not with CM of the other cell types. A slight stimulation was also obtained when tumoral MCF7 cells and fibroblasts shared the same medium but were physically separated, suggesting that close contact was required for optimal stimulation of collagen synthesis. The collagen synthesis stimulating activity was not related to a modification of fibroblast proliferation rate. The production of collagen types I, III, and VI and fibronectin were increased in cocultures of fibroblasts with MCF7 cells. The increased synthesis of collagen types I and III and fibronectin was paralleled by similar changes in the steady-state level of their mRNAs. On the contrary, the increased production of collagen type VI appeared regulated at a post-transcriptional level. [less ▲]Detailed reference viewed: 22 (2 ULg)
Characterization of regulatory functions of the varicella-zoster virus gene-63-encoded protein
Jackers, Pascale ; ; et al
in Journal of Virology (1992), 66(6), 3899-3903
Varicella-zoster virus (VZV) gene 63 encodes a protein (IE63) with a predicted molecular mass of 30.5 kDa which has amino acid similarities to the immediate-early (IE) protein 22 (ICP22) of herpes simplex ... [more ▼]
Varicella-zoster virus (VZV) gene 63 encodes a protein (IE63) with a predicted molecular mass of 30.5 kDa which has amino acid similarities to the immediate-early (IE) protein 22 (ICP22) of herpes simplex virus type 1. ICP22 is a polypeptide synthesized in herpes simplex virus type 1-infected cells, and as is the case for its VZV counterpart, its regulatory functions are unknown. On the basis of the VZV DNA sequence, it has been shown that IE63 exhibits hydrophilic and acidic properties, suggesting that this protein could play a regulatory role during the infectious cycle. We report in this article cotransfection experiments which demonstrate that the VZV gene 63 protein strongly represses, in a dose-dependent manner, the expression of VZV gene 62. On the other hand, transient expression of the VZV gene 63 protein can promote activation of the thymidine kinase gene but cannot affect the expression of the genes encoding glycoproteins I and II. The results of transient expression experiments strongly suggest that the VZV gene 63 protein could play a pivotal role in the repression of IE gene expression as well as in the activation of early gene expression [less ▲]Detailed reference viewed: 47 (20 ULg)
Effect of cell-cell and cell-matrix interactions on the response of fibroblasts to epidermal growth factor in vitro. Expression of collagen type I, collagenase, stromelysin and tissue inhibitor of metalloproteinases.
Colige, Alain ; Lambert, Charles ; Nusgens, Betty et al
in Biochemical Journal (1992), 285 ( Pt 1)
Investigations of the effect of epidermal growth factor (EGF) on the expression of four genes involved in the turnover of the extracellular matrix, collagen type I, collagenase, stromelysin and tissue ... [more ▼]
Investigations of the effect of epidermal growth factor (EGF) on the expression of four genes involved in the turnover of the extracellular matrix, collagen type I, collagenase, stromelysin and tissue inhibitor of metalloproteinases (TIMP) were performed on four strains of skin fibroblasts in vitro. Addition of EGF to subconfluent cultures for increasing periods of time up to 5 days induced an inhibition of procollagen alpha 1(I) mRNA and a strong stimulation of collagenase (100-fold) and stromelysin (1000-fold) mRNAs, whereas the mRNA of TIMP was increased to a lesser extent (5-fold). After a 40 h pulse with EGF, these effects persisted for 24-48 h after withdrawal of the growth factor and slowly diminished thereafter to attain control values after several days. By culturing fibroblasts for increasing periods of time, different levels of confluence were obtained allowing for the deposition of an extracellular biomatrix. The steady-state level of collagenase and stromelysin mRNAs were profoundly depressed in confluent as against non-confluent cultures, whereas no major change for TIMP and procollagen alpha 1(I) mRNAs was observed. Upon treatment of these cultures with EGF for 48h, the steady-state level of collagenase, stromelysin and TIMP increased, whereas procollagen alpha 1(I) mRNA was slightly reduced. These modifications were, at least in part, dependent upon a regulation of the transcription rate, as suggested from run-off experiments. Similar states of confluence were obtained by seeding cells at increasing densities in short-term cultures in which cell-cell contact predominated. In such culture conditions, the collagenase and stromelysin mRNAs were enhanced in high as compared to low density cultures. The response to EGF was progressively decreased for collagenase, stromelysin and, to a lesser extent, TIMP mRNAs at most densities and a complete lack of response to EGF at the highest cell density was observed. Under all culture conditions the modulation of collagenase mRNA was paralleled by similar modifications of enzyme activity. These results emphasize the importance of the cell-cell contacts and cell-matrix interactions in the expression of the genes coding for metalloproteinases or their inhibitor and their modulation by growth factors. [less ▲]Detailed reference viewed: 3 (2 ULg)