References of "Gilles, Christine"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailFunctional analysis of dual-specificity protein phosphatases in angiogenesis
Amand, Mathieu; ERPICUM, Charlotte ULg; Gilles, Christine ULg et al

in Pulido, Rafael (Ed.) Protein Tyrosine Phosphatases: Methods and Protocols (2016)

Therapeutic perspectives targeting angiogenesis in cancer stimulated an intense investigation of the mechanisms triggering and governing angiogenic processes. Several publications have highlighted the ... [more ▼]

Therapeutic perspectives targeting angiogenesis in cancer stimulated an intense investigation of the mechanisms triggering and governing angiogenic processes. Several publications have highlighted the importance of typical dual-specificity phosphatases (DSPs) or MKPs in endothelial cells and their role in controlling different biological functions implicated in angiogenesis such as migration, proliferation, apoptosis, tubulogenesis and cell adhesion. However, among atypical DSPs, the only one investigated in angiogenesis was DUSP3. We recently identified this DSP as new key player in endothelial cells and angiogenesis. In this chapter we provide with detailed protocols and models used to investigate the role of DUSP3 in endothelial cells and angiogenesis. We start the chapter with an overview of the role of several DSPs in angiogenesis. We continue with providing a full description of a highly efficient transfection protocol to deplete DUSP3 using small interfering RNA (siRNA) in the primary Human Umbilical Vein Endothelial Cells (HUVEC). We next describe the major assays used to investigate different processes involved in angiogenesis such as tube formation assay, proliferation assay and spheroids sprouting assay. We finish the chapter by validating our results in DUSP3-knockout mice using in vivo angiogenesis assays such as Matrigel plug and Lewis lung carcinoma cell subcutaneous xenograft model followed by anti-CD31 immunofluorescence and ex vivo aortic ring assay. All methods described can be adapted to other phosphatases and signaling molecules. [less ▲]

Detailed reference viewed: 93 (14 ULg)
Full Text
Peer Reviewed
See detailTissue factor induced by epithelial-mesenchymal transition triggers a pro-coagulant state that drives metastasis of circulating tumor cells.
Bourcy, Morgane ULg; Suarez-Carmona, Meggy ULg; Lambert, Justine ULg et al

in Cancer Research (2016)

Epithelial-mesenchymal transition (EMT) is prominent in circulating tumor cells (CTC), but how it influences metastatic spread in this setting is obscure. Insofar as blood provides a specific ... [more ▼]

Epithelial-mesenchymal transition (EMT) is prominent in circulating tumor cells (CTC), but how it influences metastatic spread in this setting is obscure. Insofar as blood provides a specific microenvironment for tumor cells, we explored a potential link between EMT and coagulation that may provide EMT-positive CTC with enhanced colonizing properties. Here we report that EMT induces tissue factor (TF), a major cell-associated initiator of coagulation and related pro-coagulant properties in the blood. TF blockade by antibody or shRNA diminished the pro-coagulant activity of EMT-positive cells, confirming a functional role for TF in these processes. Silencing the EMT transcription factor ZEB1 inhibited both EMT-associated TF expression and coagulant activity, further strengthening the link between EMT and coagulation. Accordingly, EMT-positive cells exhibited a higher persistance/survival in the lungs of mice colonized after intravenous injection, a feature diminished by TF or ZEB1 silencing. In tumor cells with limited metastatic capability, enforcing expression of the EMT transcription factor Snail increased TF, coagulant properties and early metastasis. Clinically, we identified a subpopulation of CTC expressing vimentin and TF in the blood of metastatic breast cancer patients consistent with our observations. Overall, our findings define a novel EMT-TF regulatory axis which triggers local activation of coagulation pathways to support metastatic colonization of EMT-positive CTC. [less ▲]

Detailed reference viewed: 56 (22 ULg)
Peer Reviewed
See detailEpithelial-to-mesenchymal transition (EMT)-regulated soluble factors mediate tumor angiogenesis and myeloid cell recruitment
Suarez-Carmona; Bourcy, Morgane ULg; Lesage, J et al

Conference (2015, October 13)

Detailed reference viewed: 27 (4 ULg)
Peer Reviewed
See detailControl of CXCL8/IL-8 expression by ZO-1:
Lesage, J; Suarez-Carmona, Meggy ULg; Grelet, S et al

Poster (2015, October 12)

Detailed reference viewed: 19 (0 ULg)
Full Text
Peer Reviewed
See detailThe human NANOS3 gene contributes to lung tumour invasion by inducing epithelial-mesenchymal transition
Grelet, S; Andries, V; Polette, M et al

in Journal of Pathology (The) (2015), 237(1), 25-37

Detailed reference viewed: 13 (1 ULg)
Full Text
Peer Reviewed
See detailGenetic depletion of the dual specificity protein phosphatase DUSP3 promotes LLC Lung tumour metastasis
Vandereyken, Maud ULg; Amand, Mathieu ULg; Van Overmeire, Eva et al

Conference (2015, June)

DUSP3, also called Vaccinia-H1 Related (VHR) is a small dual specificity phosphatase dephosphorylating both tyrosine and serine/threonine phosphorylated residues. DUSP3 plays an important role in cell ... [more ▼]

DUSP3, also called Vaccinia-H1 Related (VHR) is a small dual specificity phosphatase dephosphorylating both tyrosine and serine/threonine phosphorylated residues. DUSP3 plays an important role in cell cycle regulation and is up-regulated in several human cancers. The physiological role of this phosphatase is, however, poorly understood. We have recently generated a DUSP3 knockout mouse by homologous recombination. The obtained mice have no spontaneous phenotype or pathology. However, DUSP3 deficiency prevented neo-vascularization of subcutaneously transplanted Matrigel plugs and Lung Lewis Carcinoma (LLC) tumours, suggesting an involvement of DUSP3 in tumour angiogenesis. Considering the importance of angiogenesis in metastatic formation, our study aimed to investigate the role of DUSP3 in metastatic dissemination. To do so, we used the LLC experimental metastasis model that shortcuts the intravasation/extravasation processes by injecting intravenously the LLC and the B16 (metastatic melanoma cell line) cells. Surprisingly, LLC, but not B16, lung metastasis developed twice faster in DUSP3-KO than WT mice. The enhanced LLC metastatic growth in DUSP3-/- mice was transferable to WT mice via DUSP3-/- bone marrow adoptive transfer, suggesting an involvement of the hematopoietic compartment in the observed phenotype. This was confirmed by a higher infiltration of neutrophils and macrophages in the lungs of DUSP3-KO compared to WT mice after LLC injection. This infiltration was correlated with higher expression of the chemokine receptor CCR2 in LLC-bearing DUSP3-KO lungs macrophages. Interestingly, LLC, but not B16 cells, were found to secrete high level of CCL2/MCP1, the CCR ligand chemokine. In line with this observation, we found that DUSP3-/- bone marrow derived-macrophages have a higher migration potential in response to LLC, but not B16, -conditionned medium. Altogether, our results suggest that DUSP3 plays an important role in metastatic dissemination/growth by a mechanism involving the control of CCR2-CCL2 chemoattraction axis in macrophages. [less ▲]

Detailed reference viewed: 32 (4 ULg)
Full Text
Peer Reviewed
See detailGenetic depletion of the dual specificity protein phosphatase DUSP3 promotes LLC Lung tumour metastasis
Vandereyken, Maud ULg; Amand, Mathieu; Van Overmeire, Eva et al

Poster (2015, June)

DUSP3, also called Vaccinia-H1 Related (VHR) is a small dual specificity phosphatase dephosphorylating both tyrosine and serine/threonine phosphorylated residues. DUSP3 plays an important role in cell ... [more ▼]

DUSP3, also called Vaccinia-H1 Related (VHR) is a small dual specificity phosphatase dephosphorylating both tyrosine and serine/threonine phosphorylated residues. DUSP3 plays an important role in cell cycle regulation and is up-regulated in several human cancers. The physiological role of this phosphatase is, however, poorly understood. We have recently generated a DUSP3 knockout mouse by homologous recombination. The obtained mice have no spontaneous phenotype or pathology. However, DUSP3 deficiency prevented neo-vascularization of subcutaneously transplanted Matrigel plugs and Lung Lewis Carcinoma (LLC) tumours, suggesting an involvement of DUSP3 in tumour angiogenesis. Considering the importance of angiogenesis in metastatic formation, our study aimed to investigate the role of DUSP3 in metastatic dissemination. To do so, we used the LLC experimental metastasis model that shortcuts the intravasation/extravasation processes by injecting intravenously the LLC and the B16 (metastatic melanoma cell line) cells. Surprisingly, LLC, but not B16, lung metastasis developed twice faster in DUSP3-KO than WT mice. The enhanced LLC metastatic growth in DUSP3-/- mice was transferable to WT mice via DUSP3-/- bone marrow adoptive transfer, suggesting an involvement of the hematopoietic compartment in the observed phenotype. This was confirmed by a higher infiltration of neutrophils and macrophages in the lungs of DUSP3-KO compared to WT mice after LLC injection. This infiltration was correlated with higher expression of the chemokine receptor CCR2 in LLC-bearing DUSP3-KO lungs macrophages. Interestingly, LLC, but not B16 cells, were found to secrete high level of CCL2/MCP1, the CCR ligand chemokine. In line with this observation, we found that DUSP3-/- bone marrow derived-macrophages have a higher migration potential in response to LLC, but not B16, -conditionned medium. Altogether, our results suggest that DUSP3 plays an important role in metastatic dissemination/growth by a mechanism involving the control of CCR2-CCL2 chemoattraction axis in macrophages. [less ▲]

Detailed reference viewed: 20 (4 ULg)
See detailEpithelial-to-mesenchymal transitions and the metastatic spread
Gilles, Christine ULg

Conference (2015, May 14)

Detailed reference viewed: 16 (3 ULg)
See detailEpithelial-to-Mesenchymal Transitions modulate interactions between Circulating Tumor Cells and the coagulation system: implication for the metastatic spread.
Bourcy, M; Suarez-Carmona, M; Francart, ME et al

Conference (2015, May 13)

Detailed reference viewed: 14 (3 ULg)