Invasiveness

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Frédéric M. Coquelle - One of the best experts on this subject based on the ideXlab platform.

  • protein tyrosine phosphatase 4a3 ptp4a3 prl 3 promotes the aggressiveness of human uveal melanoma through dephosphorylation of crmp2
    Scientific Reports, 2019
    Co-Authors: Laura Duciel, Océane Anezo, Cécile Laurent, Nathalie Planque, Frédéric M. Coquelle, Koushik Mandal
    Abstract:

    Uveal melanoma (UM) is an aggressive tumor in which approximately 50% of patients develop metastasis. Expression of the PTP4A3 gene, encoding a phosphatase, is predictive of poor patient survival. PTP4A3 expression in UM cells increases their migration in vitro and Invasiveness in vivo. Here, we show that CRMP2 is mostly dephosphorylated on T514 in PTP4A3 expressing cells. We also demonstrate that inhibition of CRMP2 expression in UM cells expressing PTP4A3 increases their migration in vitro and Invasiveness in vivo. This phenotype is accompanied by modifications of the actin microfilament network, with shortened filaments, whereas cells with a inactive mutant of the phosphatase do not show the same behavior. In addition, we showed that the cell cytoplasm becomes stiffer when CRMP2 is downregulated or PTP4A3 is expressed. Our results suggest that PTP4A3 acts upstream of CRMP2 in UM cells to enhance their migration and Invasiveness and that a low level of CRMP2 in tumors is predictive of poor patient survival.

  • Protein tyrosine phosphatase 4A3 (PTP4A3/PRL-3) promotes the aggressiveness of human uveal melanoma through dephosphorylation of CRMP2
    Nature Publishing Group, 2019
    Co-Authors: Laura Duciel, Océane Anezo, Kalpana Mandal, Cécile Laurent, Nathalie Planque, Frédéric M. Coquelle, David Gentien, Jean-baptiste Manneville, Simon Saule
    Abstract:

    Abstract Uveal melanoma (UM) is an aggressive tumor in which approximately 50% of patients develop metastasis. Expression of the PTP4A3 gene, encoding a phosphatase, is predictive of poor patient survival. PTP4A3 expression in UM cells increases their migration in vitro and Invasiveness in vivo. Here, we show that CRMP2 is mostly dephosphorylated on T514 in PTP4A3 expressing cells. We also demonstrate that inhibition of CRMP2 expression in UM cells expressing PTP4A3 increases their migration in vitro and Invasiveness in vivo. This phenotype is accompanied by modifications of the actin microfilament network, with shortened filaments, whereas cells with a inactive mutant of the phosphatase do not show the same behavior. In addition, we showed that the cell cytoplasm becomes stiffer when CRMP2 is downregulated or PTP4A3 is expressed. Our results suggest that PTP4A3 acts upstream of CRMP2 in UM cells to enhance their migration and Invasiveness and that a low level of CRMP2 in tumors is predictive of poor patient survival

Laura Duciel - One of the best experts on this subject based on the ideXlab platform.

  • protein tyrosine phosphatase 4a3 ptp4a3 prl 3 promotes the aggressiveness of human uveal melanoma through dephosphorylation of crmp2
    Scientific Reports, 2019
    Co-Authors: Laura Duciel, Océane Anezo, Cécile Laurent, Nathalie Planque, Frédéric M. Coquelle, Koushik Mandal
    Abstract:

    Uveal melanoma (UM) is an aggressive tumor in which approximately 50% of patients develop metastasis. Expression of the PTP4A3 gene, encoding a phosphatase, is predictive of poor patient survival. PTP4A3 expression in UM cells increases their migration in vitro and Invasiveness in vivo. Here, we show that CRMP2 is mostly dephosphorylated on T514 in PTP4A3 expressing cells. We also demonstrate that inhibition of CRMP2 expression in UM cells expressing PTP4A3 increases their migration in vitro and Invasiveness in vivo. This phenotype is accompanied by modifications of the actin microfilament network, with shortened filaments, whereas cells with a inactive mutant of the phosphatase do not show the same behavior. In addition, we showed that the cell cytoplasm becomes stiffer when CRMP2 is downregulated or PTP4A3 is expressed. Our results suggest that PTP4A3 acts upstream of CRMP2 in UM cells to enhance their migration and Invasiveness and that a low level of CRMP2 in tumors is predictive of poor patient survival.

  • Protein tyrosine phosphatase 4A3 (PTP4A3/PRL-3) promotes the aggressiveness of human uveal melanoma through dephosphorylation of CRMP2
    Nature Publishing Group, 2019
    Co-Authors: Laura Duciel, Océane Anezo, Kalpana Mandal, Cécile Laurent, Nathalie Planque, Frédéric M. Coquelle, David Gentien, Jean-baptiste Manneville, Simon Saule
    Abstract:

    Abstract Uveal melanoma (UM) is an aggressive tumor in which approximately 50% of patients develop metastasis. Expression of the PTP4A3 gene, encoding a phosphatase, is predictive of poor patient survival. PTP4A3 expression in UM cells increases their migration in vitro and Invasiveness in vivo. Here, we show that CRMP2 is mostly dephosphorylated on T514 in PTP4A3 expressing cells. We also demonstrate that inhibition of CRMP2 expression in UM cells expressing PTP4A3 increases their migration in vitro and Invasiveness in vivo. This phenotype is accompanied by modifications of the actin microfilament network, with shortened filaments, whereas cells with a inactive mutant of the phosphatase do not show the same behavior. In addition, we showed that the cell cytoplasm becomes stiffer when CRMP2 is downregulated or PTP4A3 is expressed. Our results suggest that PTP4A3 acts upstream of CRMP2 in UM cells to enhance their migration and Invasiveness and that a low level of CRMP2 in tumors is predictive of poor patient survival

Nathalie Planque - One of the best experts on this subject based on the ideXlab platform.

  • protein tyrosine phosphatase 4a3 ptp4a3 prl 3 promotes the aggressiveness of human uveal melanoma through dephosphorylation of crmp2
    Scientific Reports, 2019
    Co-Authors: Laura Duciel, Océane Anezo, Cécile Laurent, Nathalie Planque, Frédéric M. Coquelle, Koushik Mandal
    Abstract:

    Uveal melanoma (UM) is an aggressive tumor in which approximately 50% of patients develop metastasis. Expression of the PTP4A3 gene, encoding a phosphatase, is predictive of poor patient survival. PTP4A3 expression in UM cells increases their migration in vitro and Invasiveness in vivo. Here, we show that CRMP2 is mostly dephosphorylated on T514 in PTP4A3 expressing cells. We also demonstrate that inhibition of CRMP2 expression in UM cells expressing PTP4A3 increases their migration in vitro and Invasiveness in vivo. This phenotype is accompanied by modifications of the actin microfilament network, with shortened filaments, whereas cells with a inactive mutant of the phosphatase do not show the same behavior. In addition, we showed that the cell cytoplasm becomes stiffer when CRMP2 is downregulated or PTP4A3 is expressed. Our results suggest that PTP4A3 acts upstream of CRMP2 in UM cells to enhance their migration and Invasiveness and that a low level of CRMP2 in tumors is predictive of poor patient survival.

  • Protein tyrosine phosphatase 4A3 (PTP4A3/PRL-3) promotes the aggressiveness of human uveal melanoma through dephosphorylation of CRMP2
    Nature Publishing Group, 2019
    Co-Authors: Laura Duciel, Océane Anezo, Kalpana Mandal, Cécile Laurent, Nathalie Planque, Frédéric M. Coquelle, David Gentien, Jean-baptiste Manneville, Simon Saule
    Abstract:

    Abstract Uveal melanoma (UM) is an aggressive tumor in which approximately 50% of patients develop metastasis. Expression of the PTP4A3 gene, encoding a phosphatase, is predictive of poor patient survival. PTP4A3 expression in UM cells increases their migration in vitro and Invasiveness in vivo. Here, we show that CRMP2 is mostly dephosphorylated on T514 in PTP4A3 expressing cells. We also demonstrate that inhibition of CRMP2 expression in UM cells expressing PTP4A3 increases their migration in vitro and Invasiveness in vivo. This phenotype is accompanied by modifications of the actin microfilament network, with shortened filaments, whereas cells with a inactive mutant of the phosphatase do not show the same behavior. In addition, we showed that the cell cytoplasm becomes stiffer when CRMP2 is downregulated or PTP4A3 is expressed. Our results suggest that PTP4A3 acts upstream of CRMP2 in UM cells to enhance their migration and Invasiveness and that a low level of CRMP2 in tumors is predictive of poor patient survival

Océane Anezo - One of the best experts on this subject based on the ideXlab platform.

  • protein tyrosine phosphatase 4a3 ptp4a3 prl 3 promotes the aggressiveness of human uveal melanoma through dephosphorylation of crmp2
    Scientific Reports, 2019
    Co-Authors: Laura Duciel, Océane Anezo, Cécile Laurent, Nathalie Planque, Frédéric M. Coquelle, Koushik Mandal
    Abstract:

    Uveal melanoma (UM) is an aggressive tumor in which approximately 50% of patients develop metastasis. Expression of the PTP4A3 gene, encoding a phosphatase, is predictive of poor patient survival. PTP4A3 expression in UM cells increases their migration in vitro and Invasiveness in vivo. Here, we show that CRMP2 is mostly dephosphorylated on T514 in PTP4A3 expressing cells. We also demonstrate that inhibition of CRMP2 expression in UM cells expressing PTP4A3 increases their migration in vitro and Invasiveness in vivo. This phenotype is accompanied by modifications of the actin microfilament network, with shortened filaments, whereas cells with a inactive mutant of the phosphatase do not show the same behavior. In addition, we showed that the cell cytoplasm becomes stiffer when CRMP2 is downregulated or PTP4A3 is expressed. Our results suggest that PTP4A3 acts upstream of CRMP2 in UM cells to enhance their migration and Invasiveness and that a low level of CRMP2 in tumors is predictive of poor patient survival.

  • Protein tyrosine phosphatase 4A3 (PTP4A3/PRL-3) promotes the aggressiveness of human uveal melanoma through dephosphorylation of CRMP2
    Nature Publishing Group, 2019
    Co-Authors: Laura Duciel, Océane Anezo, Kalpana Mandal, Cécile Laurent, Nathalie Planque, Frédéric M. Coquelle, David Gentien, Jean-baptiste Manneville, Simon Saule
    Abstract:

    Abstract Uveal melanoma (UM) is an aggressive tumor in which approximately 50% of patients develop metastasis. Expression of the PTP4A3 gene, encoding a phosphatase, is predictive of poor patient survival. PTP4A3 expression in UM cells increases their migration in vitro and Invasiveness in vivo. Here, we show that CRMP2 is mostly dephosphorylated on T514 in PTP4A3 expressing cells. We also demonstrate that inhibition of CRMP2 expression in UM cells expressing PTP4A3 increases their migration in vitro and Invasiveness in vivo. This phenotype is accompanied by modifications of the actin microfilament network, with shortened filaments, whereas cells with a inactive mutant of the phosphatase do not show the same behavior. In addition, we showed that the cell cytoplasm becomes stiffer when CRMP2 is downregulated or PTP4A3 is expressed. Our results suggest that PTP4A3 acts upstream of CRMP2 in UM cells to enhance their migration and Invasiveness and that a low level of CRMP2 in tumors is predictive of poor patient survival

Andres J P Kleinszanto - One of the best experts on this subject based on the ideXlab platform.

  • stromelysin 1 matrix metalloproteinase 3 mmp 3 expression accounts for invasive properties of human astrocytoma cell lines
    International Journal of Cancer, 2003
    Co-Authors: Javier Mercapide, Ricardo Lopez De Cicco, Javier S Castresana, Andres J P Kleinszanto
    Abstract:

    Tumor Invasiveness is an intrinsic feature of most glial tumors that accounts for their malignant and locally destructive nature. We evaluated the subcutaneous (sc) tumorigenicity and in vivo Invasiveness of 9 astrocytoma cell lines together with their respective metalloprotease activity in order to establish their biologic behavior and malignant potential. Invasiveness was assessed with an in vivo invasion assay using tracheal xenotransplants subcutaneously implanted into Scid mice. This assay permitted us to evaluate the penetration of tumor cells into the transplanted deepithelialized tracheas previously inoculated with either normal primary glial cells or with astrocytoma-derived cell lines. Although only 2 cell lines were tumorigenic after sc inoculation, 5 out of 9 tumor cell lines were tumorigenic in the tracheal graft system. The astrocytoma cell lines showed varying levels of penetration into the tracheal wall. The tumor lines GOS3, M059K, CCFSTTG1 and A172, as well as primary normal astrocytes, were nontumorigenic and noninvasive in this experimental model. LN405, SW1088 and SW1783 cells that were not tumorigenic as sc xenotransplants, on the other hand, grew well in the tracheal graft system showing low levels of in vivo Invasiveness. U87MG and U118MG cells were tumorigenic as sc xenotransplants and showed high levels of Invasiveness. In parallel to these in vivo studies, the constitutive levels of secreted gelatinases and stromelysins (MMP-3 and MMP-11) were investigated using conditioned media submitted to gelatin or casein-substrate zymography and Western blot analysis. Neither the gelatinases (MMP-2 and MMP-9) nor MMP-11 showed a direct correlation with the levels of in vivo tumor cell Invasiveness. Conversely, secretion of MMP-3 correlated closely with tumorigenicity and Invasiveness. In vitro tumor cell Invasiveness was significantly reduced after incubation with the metalloproteinase inhibitor GM6001. This positive correlation between MMP-3 and the depth of tracheal wall penetration led us to conclude that the invasive properties of brain tumor cells may be due to the direct or indirect proteolytic effects of MMP-3 on extracellular matrix (ECM) macromolecules and that this enzyme might be a potential target for future therapies.

  • stromelysin 1 matrix metalloproteinase 3 mmp 3 expression accounts for invasive properties of human astrocytoma cell lines
    International Journal of Cancer, 2003
    Co-Authors: Javier Mercapide, Ricardo Lopez De Cicco, Javier S Castresana, Andres J P Kleinszanto
    Abstract:

    Tumor Invasiveness is an intrinsic feature of most glial tumors that accounts for their malignant and locally destructive nature. We evaluated the subcutaneous (sc) tumorigenicity and in vivo Invasiveness of 9 astrocytoma cell lines together with their respective metalloprotease activity in order to establish their biologic behavior and malignant potential. Invasiveness was assessed with an in vivo invasion assay using tracheal xenotransplants subcutaneously implanted into Scid mice. This assay permitted us to evaluate the penetration of tumor cells into the transplanted deepithelialized tracheas previously inoculated with either normal primary glial cells or with astrocytoma-derived cell lines. Although only 2 cell lines were tumorigenic after sc inoculation, 5 out of 9 tumor cell lines were tumorigenic in the tracheal graft system. The astrocytoma cell lines showed varying levels of penetration into the tracheal wall. The tumor lines GOS3, M059K, CCFSTTG1 and A172, as well as primary normal astrocytes, were nontumorigenic and noninvasive in this experimental model. LN405, SW1088 and SW1783 cells that were not tumorigenic as sc xenotransplants, on the other hand, grew well in the tracheal graft system showing low levels of in vivo Invasiveness. U87MG and U118MG cells were tumorigenic as sc xenotransplants and showed high levels of Invasiveness. In parallel to these in vivo studies, the constitutive levels of secreted gelatinases and stromelysins (MMP-3 and MMP-11) were investigated using conditioned media submitted to gelatin or casein-substrate zymography and Western blot analysis. Neither the gelatinases (MMP-2 and MMP-9) nor MMP-11 showed a direct correlation with the levels of in vivo tumor cell Invasiveness. Conversely, secretion of MMP-3 correlated closely with tumorigenicity and Invasiveness. In vitro tumor cell Invasiveness was significantly reduced after incubation with the metalloproteinase inhibitor GM6001. This positive correlation between MMP-3 and the depth of tracheal wall penetration led us to conclude that the invasive properties of brain tumor cells may be due to the direct or indirect proteolytic effects of MMP-3 on extracellular matrix (ECM) macromolecules and that this enzyme might be a potential target for future therapies. © 2003 Wiley-Liss, Inc.