References of "Invasion & Metastasis"
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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 detailModulation of the Expression of Interstitial and Type-Iv Collagenases in Coculture of Ht1080 Fibrosarcoma Cells and Fibroblasts
Munaut, Carine ULg; Noël, Agnès ULg; Weidle, U. H. et al

in Invasion & Metastasis (1995), 15(5-6), 169-78

Members of the metalloproteinase family (MMPs) are known to play a crucial role in the metastatic cascade. Here, we report some investigations about the synthesis of interstitial and type-IV collagenases ... [more ▼]

Members of the metalloproteinase family (MMPs) are known to play a crucial role in the metastatic cascade. Here, we report some investigations about the synthesis of interstitial and type-IV collagenases (gelatinases A and B) in a model of coculture of human fibroblasts and HT 1080 fibrosarcoma cells. The interstitial collagenase activity, mainly found in the conditioned medium of fibroblasts, and its mRNA level were increased in the in vitro coculture model. In contrast, gelatinase A was produced by both cell types. The HT 1080 cells additionally synthesised gelatinase B. In coculture, an enhancement of gelatinase A and the presence of its activated form were observed. Northern blot analysis demonstrated that this enzymatic enhancement occurred at a pretranslational level. The stimulation of the interstitial collagenase activity was partially mediated through soluble factor(s), whereas increased gelatinase A appeared to require direct cell-cell interactions. The extracellular matrix component, type-I collagen, stimulated the enzymatic activities released by the individual cells, but it did not modulate the synthesis of interstitial collagenase in coculture. Our results demonstrate that distinct MMPs are modulated by distinct mechanisms, all depending on specific interactions between tumour cells and host fibroblasts. [less ▲]

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See detailReevaluation by Image Analysis of the Effects of Fibroblasts, Fibronectin or Laminin Upon Colony Formation in Mouse Lungs by B16 Melanoma Cells
Coucke, P. H.; Lambertz, M.; Baramova, E. N. et al

in Invasion & Metastasis (1993), 13(4), 201-11

A recently described personal method based on image analysis of histological sections was used in order to quantify lung colony formation by B16 melanoma cells injected intravenously into the mouse. These ... [more ▼]

A recently described personal method based on image analysis of histological sections was used in order to quantify lung colony formation by B16 melanoma cells injected intravenously into the mouse. These tumor cells were preincubated in vitro either with fibronectin (FN), laminin (LN) or fibroblasts (FB), which are implicated in the process of invasion and metastasis. Thanks to this method, a more accurate analysis of lung colonies (section area and number) formed by tumor cells was realized. By image analysis, we show that when FB were mixed with B16 cells, a drastic increase of tumor sections number and area was induced. LN increased the tumor sections area, but not their number. No effect of FN on B16 cells was observed. LN and FN promoted tumor anchorage in the depth of the lungs while FB reduced the latter. These facts could explain the contradictory results obtained by simply counting macroscopically superficial lung colonies. When cultured in vitro, these B16 melanoma cells did not produce any type of IV collagenase, either alone or in the presence of LN or FN, but in cocultures (B16 with 3T3) and in fibroblasts cultures, this enzyme was present. This could explain, among other factors, why the rate of invasiveness exerted by B16 cells is higher when the latter are coinjected with FB. [less ▲]

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See detailDifferent Mechanisms of Extracellular Matrix Remodeling by Fibroblasts in Response to Human Mammary Neoplastic Cells
Noël, Agnès ULg; Munaut, Carine ULg; Nusgens, Betty ULg et al

in Invasion & Metastasis (1993), 13(2), 72-81

Human breast tumors are often associated with a fibrotic reaction termed desmoplasia. Tumor cells may indirectly modulate the composition of the extracellular matrix by influencing fibroblast properties ... [more ▼]

Human breast tumors are often associated with a fibrotic reaction termed desmoplasia. Tumor cells may indirectly modulate the composition of the extracellular matrix by influencing fibroblast properties. They may also directly interact with collagen fibrils leading to retraction of the matrix. We have studied in vitro the influence of various human mammary tumor cells on the proliferation rate of normal human fibroblasts and on their level of collagen synthesis, as well as their release of collagenase activity. Interactions between neoplastic cells and collagen matrix were investigated by incorporation of tumor cells in collagen gels (lattices) and measurement of their retraction. All cells tested (HBL100, SW613, SA52, MDA-MB-231, MCF7, MCF7/6, MCF7 ras, BT20 and T47D) were able to modulate the composition of the extracellular matrix by one or several of the mechanisms investigated. Our results also demonstrate an opposite regulation of collagen and collagenase production. The effects on the collagen metabolism and on fibroblast proliferation are probably mediated by soluble cytokines since they are reproduced by incubating the fibroblasts in the presence of medium conditioned by tumor cells. The desmoplastic reaction may thus result from different mechanisms dependent upon tumor cell types. [less ▲]

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See detailStimulation of the 92-Kd Type Iv Collagenase Promoter and Enzyme Expression in Human Melanoma Cells
Lauricella-Lefebvre, M. A.; Castronovo, Vincenzo ULg; Sato, H. et al

in Invasion & Metastasis (1993), 13(6), 289-300

The 92-kD type IV collagenase is a member of the metalloproteinase family which degrades type IV collagen, a major component of basement membrane and is involved in tumor invasion and metastasis. The ... [more ▼]

The 92-kD type IV collagenase is a member of the metalloproteinase family which degrades type IV collagen, a major component of basement membrane and is involved in tumor invasion and metastasis. The promoter and adjacent regulatory sequences of the 92-kD type IV collagenase have been identified previously and three cis-acting elements homologous to the binding sites for AP-1, NF-KB and SP-1 proteins contributed to induction of the promoter activity by 12-O-tetradecanoylphorbol 13-acetate (TPA) and tumor necrosis factor (TNF-alpha) in HT1080 cells. To date, no direct correlation between promoter activity and expression of the 92-kD type IV collagenase has been reported in normal or cancer cells. In this study, the effects of the transcriptional stimulation of the 92-kD type IV collagenase gene on the expression of the enzyme in human A2058 melanoma cells was analyzed by zymography experiments. Quantitative immunoblots using a monoclonal antibody that recognized specifically and exclusively the 92-kD type IV collagenase, confirmed that the 92-kD gelatinase was 92-kD type IV collagenase. Stimulation of the promoter activity resulted in increased gelatinase activity in the culture medium of A2058 cells. A direct correlation between TPA- and TNF-alpha-mediated promoter stimulation of the 92-kD type IV collagenase gene and its expression was also demonstrated in the human fibrosarcoma HT1080 cells. Interleukin-1 alpha failed to induce 92-kD gene promoter activity and type IV collagenase expression in melanoma and fibrosarcoma cell lines. Our data demonstrated that TPA- and TNF-alpha-induced 92-kD type IV collagenase promoter stimulation leads to a proportional increase of enzyme expression and secretion and thus could contribute to the activation of the invasive phenotype. [less ▲]

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See detailLaminin Receptors and Laminin-Binding Proteins During Tumor Invasion and Metastasis
Castronovo, Vincenzo ULg

in Invasion & Metastasis (1993), 13(1), 1-30

Interactions between cancer cells and laminin, a major component of basement membranes, play a critical role at several steps of the complex process of tumor invasion and metastasis. These interactions ... [more ▼]

Interactions between cancer cells and laminin, a major component of basement membranes, play a critical role at several steps of the complex process of tumor invasion and metastasis. These interactions are mediated through a large variety of cell surface proteins designated as laminin receptors and/or laminin-binding proteins. The growing number of identified laminin binding proteins and domains of this glycoprotein that are biologically active illustrate the complexity of cellular interactions with laminin. The 67-kD laminin receptor (67 LR) was the first protein identified in 1983 as a high-affinity laminin receptor, and its expression is dramatically increased in a large variety of cancer cells. The 67 LR is the subject of several controversies and confusion generated mainly by two events. First, the identification of several new laminin-binding proteins has raised the difficult task of attributing specific functions to specific receptors in contrast to initial beliefs that all cellular laminin-driven biological activities were mediated through the 67 LR. The second source of controversy is the large molecular-weight discrepancy between the 37-kD polypeptide encoded by the 67 LR cDNA clone and the mature 67 LR. In this manuscript, a critical and extensive review of the data accumulated on the 67 LR is presented regarding both its molecular structure and its role during tumor invasion and metastasis. A hypothetical model of the 67 LR is also proposed. Since the first identification of the 67 LR, at least 14 other cell surface molecules have been reported to be potential laminin receptors or laminin-binding proteins. These include members of the beta-galactoside-binding lectin family, seven members of the integrin family, the galactosyltransferase and some not yet fully characterized cell surface molecules. These laminin receptors and laminin-binding proteins are also described and their functions are also discussed with a particular emphasis on their participation in the constitution of the invasive phenotype. [less ▲]

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See detailEvaluation of in Vitro Reconstituted Basement Membrane Assay to Assess the Invasiveness of Tumor Cells
Simon, N.; Noël, Agnès ULg; Foidart, Jean-Michel ULg

in Invasion & Metastasis (1992), 12(3-4), 156-67

The crossing of tumor cells through basement membranes represents a critical step in the metastatic process. We have used a reconstituted basement membrane (matrigel) coated on filter in a Boyden chamber ... [more ▼]

The crossing of tumor cells through basement membranes represents a critical step in the metastatic process. We have used a reconstituted basement membrane (matrigel) coated on filter in a Boyden chamber to assess the invasive potential of tumor and normal cells. No correlation was found between chemoinvasion in vitro and the metastatic potential in vivo. Normal human fibroblasts and murine 3T3 fibroblasts penetrated filters coated with matrigel. On the other hand, the tumoral cells (MCF7, MCF7 gpt, MCF7 ras, BeWo, JAR, NUC-1 cells) were unable to cross the matrix. Our results suggest that in our conditions, this widely used model to assess tumoral invasion does not provide a universal assay to test the invasiveness of tumor cells. Penetration of the matrigel appears to be related to chemotactic or haptotactic responses depending upon cell types. Our data emphasize the variability of molecular events associated with basement membrane invasion. [less ▲]

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See detailType Iv and Interstitial Collagenolytic Activities in Normal and Malignant Trophoblast Cells Are Specifically Regulated by the Extracellular Matrix
Emonard, H.; Christiane, Y.; Smet, M. et al

in Invasion & Metastasis (1990), 10(3), 170-7

Type IV and interstitial collagenolytic activities were compared in human malignant and normal trophoblast cells cultured on plastic, in presence or absence of laminin in solution, on matrigel (a gel of ... [more ▼]

Type IV and interstitial collagenolytic activities were compared in human malignant and normal trophoblast cells cultured on plastic, in presence or absence of laminin in solution, on matrigel (a gel of basement membrane components) and on type I collagen gel. Laminin highly stimulated the type IV collagenolytic activity but not the interstitial collagenolytic activity, in malignant trophoblast cells. This glycoprotein had no effect on the interstitial collagenolytic activity and doubled the type IV collagenolytic activity in normal trophoblast cells. Thus malignant trophoblast cells produce preferentially the enzyme able to degrade basement membrane when in contact with laminin, and the enzyme able to degrade interstitial collagen fibers when cultured on type I collagen. On the contrary, type I collagen gel and matrigel equally increased both type IV and interstitial collagenolytic activities by normal trophoblast cells. Interactions of tumor trophoblast or normal trophoblast cells with the extracellular matrix result thus in distinct stimulations of collagenolytic activities. Increased production of type IV collagenolytic activity upon exposure to laminin appears to be specific of the metastatic phenotype. [less ▲]

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See detailPerfusion of Human Umbilical Veins. A New Approach to Study the Interactions of Circulating Malignant Cells with Vascular Wall and Their Modulations
Castronovo, Vincenzo ULg; Parent, B.; Foidart, Jean-Michel ULg et al

in Invasion & Metastasis (1988), 8(6), 332-50

Interactions of malignant or non-malignant human and rodent cells with the vascular wall were studied using perfused human umbilical cord veins. The integrity of perfused endothelium was confirmed by ... [more ▼]

Interactions of malignant or non-malignant human and rodent cells with the vascular wall were studied using perfused human umbilical cord veins. The integrity of perfused endothelium was confirmed by morphological and functional criteria. Highly malignant cells in vivo adhered to the endothelial cells, as shown by scanning electron microscopy. The specific attachment of radiolabelled malignant cells to the whole vein was already maximal within 30-60 min and remained stable for perfusion flow rates ranging between 10 and 60 ml/min. It increased proportionally to the number of cells infused and could be modulated by human platelets, human fibronectin and rabbit anti-laminin antibodies. In contrast, the binding of human or rodent non-malignant cells in vivo, of human red blood cells and of human platelets to the endothelial cells was negligible under similar experimental conditions. This perfusion system therefore represents a new model for elucidating some mechanisms involved in tumour cell arrest in vivo. [less ▲]

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See detailHuman Anti-Alpha-Galactosyl Igg Reduces the Lung Colonization by Murine Mo4 Cells
Castronovo, Vincenzo ULg; Foidart, Jean-Michel ULg; Li Vecchi, M. et al

in Invasion & Metastasis (1987), 7(6), 325-45

The lung colonization of MO4 cells, a highly malignant murine cell line, is strongly reduced in syngeneic C3H/He mice by a prior incubation with anti-alpha-galactosyl antibody (alpha-Gal Ab), a natural ... [more ▼]

The lung colonization of MO4 cells, a highly malignant murine cell line, is strongly reduced in syngeneic C3H/He mice by a prior incubation with anti-alpha-galactosyl antibody (alpha-Gal Ab), a natural IgG antibody present in high titers in all normal human sera and specifically recognizing Gal alpha(1----3) structures (alpha-D-galactopyranosyl; alpha-D-Galp). The protective effect is due to a binding of alpha-Gal Ab to alpha-D-Galp end groups of MO4 cells, inducing both an increase in their sequestration into the liver and the spleen and a decrease in their sequestration into the lung. The F(ab')2 fragments of this antibody also exhibit a protective effect by inhibiting the homing of MO4 cells into the lung, without modifying their accumulation into the spleen and the liver. Since both the antibody and the alpha-galactosidase pretreatments of MO4 cells block their subsequent attachment to murine laminin in vitro, we suggest that, in this model, the lung colonization may be dependent on the alpha-D-Galp end groups exposed on the surface of MO4 cells. [less ▲]

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