References of "Gilles, Christine"
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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 (in press)

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 ▲]

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See detailRegulation of Tissue Factor by Epithelial-to-Mesenchymal Transitions: Impacts for the metastatic progression.
Francart; Bourcy, M; Suarez-Carmona, M et al

Poster (2015, December 03)

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See detailEpithelial-to-mesenchymal transition (EMT)-regulated soluble factors mediate tumor angiogenesis and myeloid cell recruitment
Suarez-Carmona, M; Bourcy, M; Lesage, J et al

Conference (2015, October 13)

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See detailControl of CXCL8/IL-8 expression by ZO-1:
Lesage, J; Suarez-Carmona, Meggy ULg; Grelet, S et al

Poster (2015, October 12)

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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

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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 ▲]

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See detailRegulation of Tissue Factor by Epithelial-to-Mesenchymal Transitions: Impacts for the metastatic progression.
Francart, ME; Bourcy, M; Lambert, J et al

Poster (2015, May 13)

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See detailEpithelial-to-mesenchymal transitions and the metastatic spread
Gilles, Christine ULg

Conference (2015, May 13)

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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)

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See detailMesenchymal stem cells shed amphiregulin at the surface of lung carcinoma cells in a juxtacrine manner .
Carnet, Oriane ULg; Lecomte, Julie; Masset, Anne et al

in Neoplasia : An International Journal for Oncology Research (2015), 17(7), 552-63

Solid tumors comprise cancer cells and different supportive stromal cells, including mesenchymal stem cells (MSCs), which have recently been shown to enhance tumor growth and metastasis. We provide new ... [more ▼]

Solid tumors comprise cancer cells and different supportive stromal cells, including mesenchymal stem cells (MSCs), which have recently been shown to enhance tumor growth and metastasis. We provide new mechanistic insights into how bone marrow (BM)-derived MSCs co-injected with Lewis lung carcinoma cells promote tumor growth and metastasis in mice. The proinvasive effect of BM-MSCs exerted on tumor cells relies on an unprecedented juxtacrine action of BM-MSC, leading to the trans-shedding of amphiregulin (AREG) from the tumor cell membrane by tumor necrosis factor-α-converting enzyme carried by the BM-MSC plasma membrane. The released soluble AREG activates cancer cells and promotes their invasiveness. This novel concept is supported by the exploitation of different 2D and 3D culture systems and by pharmacological approaches using a tumor necrosis factor-α-converting enzyme inhibitor and AREG-blocking antibodies. Altogether, we here assign a new function to BM-MSC in tumor progression and establish an uncovered link between AREG and BM-MSC. [less ▲]

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See detailVimentin-ERK Signaling Uncouples Slug Gene Regulatory Function.
Virtakoivu, Reetta; Mai, Anja; Mattila, Elina et al

in Cancer research (2015), 75(11), 2349-62

Epithelial-mesenchymal transition (EMT) in cells is a developmental process adopted during tumorigenesis that promotes metastatic capacity. In this study, we advance understanding of EMT control in cancer ... [more ▼]

Epithelial-mesenchymal transition (EMT) in cells is a developmental process adopted during tumorigenesis that promotes metastatic capacity. In this study, we advance understanding of EMT control in cancer cells with the description of a novel vimentin-ERK axis that regulates the transcriptional activity of Slug (SNAI2). Vimentin, ERK, and Slug exhibited overlapping subcellular localization in clinical specimens of triple-negative breast carcinoma. RNAi-mediated ablation of these gene products inhibited cancer cell migration and cell invasion through a laminin-rich matrix. Biochemical analyses demonstrated direct interaction of vimentin and ERK, which promoted ERK activation and enhanced vimentin transcription. Consistent with its role as an intermediate filament, vimentin acted as a scaffold to recruit Slug to ERK and promote Slug phosphorylation at serine-87. Site-directed mutagenesis established a requirement for ERK-mediated Slug phosphorylation in EMT initiation. Together, these findings identified a pivotal step in controlling the ability of Slug to organize hallmarks of EMT. [less ▲]

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See detailSoluble factors regulated by epithelial-mesenchymal transition mediate tumour angiogenesis and myeloid cell recruitment.
Suarez-Carmona, Meggy ULg; Bourcy, Morgane ULg; LESAGE, J et al

in Journal of Pathology (The) (2015)

Epithelial-to-mesenchymal transition (EMT) programs provide cancer cells with invasive and survival capacities that might favor metastatic dissemination. Whilst signaling cascades triggering EMT have been ... [more ▼]

Epithelial-to-mesenchymal transition (EMT) programs provide cancer cells with invasive and survival capacities that might favor metastatic dissemination. Whilst signaling cascades triggering EMT have been extensively studied, the impact of EMT on the crosstalk between tumor cells and the tumor microenvironment remains elusive. We aimed to identify EMT-regulated soluble factors that facilitate the recruitment of host cells in the tumor. Our findings indicate that EMT phenotypes relate to the induction of a panel of secreted mediators, namely IL-8, IL-6, sICAM-1, PAI-1 and GM-CSF, and implicate the EMT-transcription factor Snail as a regulator of this process. We further show that EMT-derived soluble factors are pro-angiogenic in vivo (in the mouse ear sponge assay), ex vivo (in the rat aortic ring assay) and in vitro (in a chemotaxis assay). Additionally, conditioned medium from EMT-positive cells stimulates the recruitment of myeloid cells. In a bank of 40 triple-negative breast cancers, tumors presenting features of EMT were significantly more angiogenic and infiltrated by a higher quantity of myeloid cells compared to tumors with little or no EMT. Taken together, our results show that EMT programs trigger the expression of soluble mediators in cancer cells that stimulate angiogenesis and recruit myeloid cells in vivo, which might in turn favor cancer spread. [less ▲]

Detailed reference viewed: 65 (23 ULg)