A5045091637- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- Advanced Breast Cancer Therapies
- Angiogenesis and VEGF in Cancer
- Breast Cancer Treatment Studies
- Cancer, Lipids, and Metabolism
- Cancer Treatment and Pharmacology
- Blood Coagulation and Thrombosis Mechanisms
- Cell Adhesion Molecules Research
- Metabolomics and Mass Spectrometry Studies
- HER2/EGFR in Cancer Research
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Estrogen and related hormone effects
- Signaling Pathways in Disease
- Cardiac Ischemia and Reperfusion
- Colorectal Cancer Treatments and Studies
- Cancer-related Molecular Pathways
- Advanced Proteomics Techniques and Applications
- RNA modifications and cancer
- Lung Cancer Treatments and Mutations
- Lymphatic System and Diseases
- DNA Repair Mechanisms
- Organ Transplantation Techniques and Outcomes
University of Liège
2016-2025
Weatherford College
2022
Laboratoire de Biologie du Développement
2021
University of British Columbia
2016
Anna Needs Neuroblastoma Answers
2012
Sanford Burnham Prebys Medical Discovery Institute
2009
Cancer Research Center
2009
Institute for Medical Research
2009
University of California, San Francisco
2007-2008
Cancer Research Institute
2007
Tumor recurrence is a major clinical issue that represents the principal cause of cancer-related deaths, with few targetable common pathways. Mechanisms by which residual tumors persist and progress under continuous shift between hypoxia-reoxygenation after neoadjuvent-therapy are unknown. In this study, we investigated role lipid metabolism tumor redox balance in recurrence. Lipidomics, proteomics mass spectrometry imaging approaches where applied to mouse models Genetic pharmacological...
Membrane type 1 metalloprotease (MT1-MMP) is a transmembrane that plays major role in the extracellular matrix remodeling, directly by degrading several of its components and indirectly activating pro-MMP2. We investigated effects MT1-MMP overexpression on vitro vivo properties human breast adenocarcinoma MCF7 cells, which do not express or MMP-2. MMP-2 cDNAs were either transfected alone cotransfected. All clones overexpressing 1) able to activate endogenous exogenous pro-MMP-2, 2)...
Cancer-associated fibroblasts (CAFs) are key actors in modulating the progression of many solid tumors such as breast cancer (BC). Herein, we identify an integrin α11/PDGFRβ+ CAF subset displaying tumor-promoting features BC. In preclinical MMTV-PyMT mouse model, α11-deficiency led to a drastic reduction tumor and metastasis. A clear association between α11 PDGFRβ was found at both transcriptional histological levels BC specimens. High stromal α11/PDGFRβ expression associated with high...
Triple-negative breast cancer xenografts with BRCAness, high expression of SLFN11, and RB1 loss are highly sensitive to topoisomerase I inhibitors.
Abstract Purpose: The implication of matrix metalloproteinases (MMPs) in the major stages cancer progression has fueled interest design synthetic MMP inhibitors (MMPIs) as a novel anticancer therapy. Thus far, drugs used clinical trials are broad-spectrum MMPIs therapeutic index which proved disappointingly low. development selective for tumor progression-associated MMPs is, thus, likely to offer improved possibilities. Experimental Design: anti-invasive capacity series pyrimidine-trione...
Membrane-type 1 matrix metalloproteinase (MT1-MMP) and vascular endothelial growth factor (VEGF) are two key molecules involved in pericellular proteolysis cell proliferation during tumor angiogenesis. Our previous data showed that MT1-MMP overexpression human breast carcinoma MCF7 cells induced an up-regulation of VEGF expression. This effect was associated vivo with accelerated We now provide evidence specifically affected VEGF-A production failed to influence other family members (VEGF,...
Membrane type-1 matrix metalloproteinase (MT1-MMP) is an activator of soluble MMP-2. The activity both MMPs regulated by their physiological inhibitor TIMP-2. An MT1-MMP/MMP-2/TIMP-2 axis plays a key role in the invasive behavior many cell types. Despite its importance, epigenetic control this pro-invasive insufficiently studied, and, as result, modification rational and clinically beneficial manner exceedingly difficult. Therefore, we performed analysis MT1-MMP, MMP-2, TIMP-2 gene promoters...
Processes such as cell proliferation, angiogenesis, apoptosis, or invasion are strongly influenced by the surrounding microenvironment of tumor. Therefore, ability to change these surroundings represents an important property through which tumor cells able acquire specific functions necessary for growth and dissemination. Matrix metalloproteinases (MMPs) constitute key players in this process, allowing modify extracellular matrix (ECM) release cytokines, factors, other cell-surface...
Innate regulatory networks within organs maintain tissue homeostasis and facilitate rapid responses to damage. We identified a novel pathway regulating vessel stability in tissues that involves matrix metalloproteinase 14 (MMP14) transforming growth factor beta 1 (TGFβ1). Whereas plasma proteins rapidly extravasate out of vasculature wild-type mice following acute damage, short-term treatment vivo with broad-spectrum inhibitor, neutralizing antibodies TGFβ1, or an activin-like kinase 5...
The development of vascular system depends on the coordinated activity a number distinct families molecules including growth factors and their receptors, cell adhesion molecules, extracellular matrix (ECM) proteolytic enzymes. Matrix metalloproteases (MMPs) are family ECM degrading enzymes required for both physiological pathological angiogenesis. Increasing evidence, point to direct role membrane type-MMPs (MT-MMPs) in stabilization, maturation, leakage. Our understanding nature MT-MMP...
Purpose.: To evaluate the antilymphangiogenic potential of multi-target tyrosine kinase inhibitor sunitinib in corneal neovascularization (NV). Methods.: Inflammatory NV was induced by thermal cauterization applied central cornea mice, to which malate daily administered gavage or not. At days 6, 11, 17 post cauterization, lymphatic and blood vessels, as well inflammatory cells were immunostained quantified whole-mounted corneas. RT-PCRs performed evidence VEGF–A, VEGF-C, VEGF-D, placental...
Purpose: Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy have a poor outcome. We developed patient-derived xenografts (PDX) from tumors to identify efficient chemotherapies and predictive biomarkers in context of resistance anthracyclines- taxanes-based treatments.Experimental Design: PDX were established primary treated setting. TNBC by anthracyclines, taxanes, platins, capecitabine. Predictive identified transcriptomic immunohistologic...
Abstract Purpose: Here, we investigated the clinical relevance of an unprecedented combination three biomarkers in triple-negative breast cancer (TNBC), both human samples and patient-derived xenografts TNBC (PDX-TNBC): EGFR, its recently identified partner (MT4-MMP), retinoblastoma protein (RB). Experimental Design: IHC analyses were conducted on PDX-TNBC to evaluate production biomarkers. The sensitivity cells expressing or not MT4-MMP anti-EGFR (erlotinib) anti-CDK4/6 inhibitor...
Metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer often develops resistance to first-line treatment, typically combining cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) with therapy (HT) [1, 2]. After an initial response, most patients become resistant, compensatory mechanisms are not fully uncovered [3]. To address this, we analyzed HR+ resistant CAMA1 747D cells using whole-exome RNA sequencing, supplemented by...
Tissue inhibitor of metalloproteinase 2 (TIMP-2) is required for the membrane type 1 matrix (MT1-MMP)-dependent activation pro-MMP-2 on cell surface. MT1-MMP-bound TIMP-2 has been shown to function as a receptor secreted pro-MMP-2, resulting in formation trimolecular complex. In presence uncomplexed active MT1-MMP, prodomain surface-associated MMP-2 cleaved, and activated released. However, behavior during currently unknown. this study,125I-labeled recombinant (125I-rTIMP-2) was used...
Abstract Membrane-type matrix metalloproteinases (MT-MMP) constitute a subfamily of six distinct membrane-associated MMPs. Although the contribution MT1-MMP during different steps cancer progression has been well documented, significance other MT-MMPs is rather unknown. We have investigated involvement MT4-MMP, glycosylphosphatidylinositol–anchored protease, in breast progression. Interestingly, immunohistochemical analysis shows that MT4-MMP production at protein level strongly increased...