References of "Cataldo, Didier"
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See detailDusp3 deletion in mice promotes experimental lung tumour metastasis in a macrophage dependent manner
Vandereyken, Maud; Jacques, Sophie; Van Overmeire, Eva et al

in PLoS ONE (2017)

Vaccinia-H1 Related (VHR) dual-specificity phosphatase, or DUSP3, plays an important role in cell cycle regulation and its expression is altered in several human cancers. In mouse model, DUSP3 deletion ... [more ▼]

Vaccinia-H1 Related (VHR) dual-specificity phosphatase, or DUSP3, plays an important role in cell cycle regulation and its expression is altered in several human cancers. In mouse model, DUSP3 deletion prevents neo-angiogenesis and b-FGF-induced microvessel out- growth. Considering the importance of angiogenesis in metastasis formation, our study aimed to investigate the role of DUSP3 in tumour cell dissemination. Using a Lewis Lung carcinoma (LLC) experimental metastasis model, we observed that DUSP3-/- mice devel- oped larger lung metastases than littermate controls. DUSP3-/- bone marrow transfer to lethally irradiated DUSP3+/+ mice was sufficient to transfer the phenotype to DUSP3+/+ mice, indicating that hematopoietic cells compartment was involved in the increased tumour cell dissemination to lung tissues. Interestingly, we found a higher percentage of tumour- promoting Ly6Cint macrophages in DUSP3-/- LLC-bearing lung homogenates that was at least partially due to a better recruitment of these cells. This was confirmed by 1) the pres- ence of higher number of the Ly6Bhi macrophages in DUSP3-/- lung homogenates and by 2) the better migration of DUSP3-/- bone marrow sorted monocytes, peritoneal macrophages and bone marrow derived macrophages (BMDMs), compared to DUSP3+/+ monocytes, macrophages and BMDMs, in response to LLC-conditioned medium. Our study demon- strates that DUSP3 phosphatase plays a key role in metastatic growth through a mechanism involving the recruitment of macrophages towards LLC-bearing lungs. [less ▲]

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See detailEMT and inflammation: inseparable actors of cancer progression.
Suarez-Carmona, Meggy; Lesage, Julien; Cataldo, Didier ULiege et al

in Molecular Oncology (2017)

Tumors can be depicted as wounds that never heal, and are infiltrated by a large array of inflammatory and immune cells. Tumor-associated chronic inflammation is a hallmark of cancer that fosters ... [more ▼]

Tumors can be depicted as wounds that never heal, and are infiltrated by a large array of inflammatory and immune cells. Tumor-associated chronic inflammation is a hallmark of cancer that fosters progression to a metastatic stage, as has been extensively reviewed lately. Indeed, inflammatory cells persisting in the tumor establish a cross-talk with tumor cells that may result in a phenotype switch into tumor-supporting cells. This has been particularly well described for macrophages and is referred to as tumor-associated "M2" polarization. Epithelial-to-mesenchymal transition (EMT), the embryonic program that loosens cell-cell adherence complexes and endows cells with enhanced migratory and invasive properties, can be co-opted by cancer cells during metastatic progression. Cancer cells that have undergone EMT are more aggressive, displaying increased invasiveness, stem-like features and resistance to apoptosis. EMT programs can also stimulate the production of pro-inflammatory factors by cancer cells. Conversely, inflammation is a potent inducer of EMT in tumors. Therefore, the two phenomena may sustain each other, in an alliance for metastasis. This is the focus of this review, where the interconnections between EMT programs and cellular and molecular actors of inflammation are described. We also recapitulate data linking the EMT/inflammation axis to metastasis. [less ▲]

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See detailChanges in biophysical membrane properties induced by the Budesonide/ Hydroxy-β-cyclodextrin complex
dos Santos, Andreia; Bayiha, Jules; Dufour, Gilles et al

in BBA Biomembranes (2017)

Budesonide (BUD), a poorly soluble anti-inflammatory drug, is used to treat patients suffering from asthma and COPD (Chronic Obstructive Pulmonary Disease). Hydroxypropyl-β-cyclodextrin (HPβCD), a ... [more ▼]

Budesonide (BUD), a poorly soluble anti-inflammatory drug, is used to treat patients suffering from asthma and COPD (Chronic Obstructive Pulmonary Disease). Hydroxypropyl-β-cyclodextrin (HPβCD), a biocompatible cyclodextrin known to interact with cholesterol, is used as a drug-solubilizing agent in pharmaceutical formulations. Budesonide administered as an inclusion complex within HPβCD (BUD:HPβCD) required a quarter of the nominal dose of the suspension formulation and significantly reduced neutrophil induced inflammation in a COPD mouse model exceeding the effect of each molecule administered individually. This suggests the role of lipid domains enriched in cholesterol for inflammatory signaling activation. In this context, we investigated the effect of BUD:HPβCD on the biophysical properties of membrane lipids. On cellular models (A549, lung epithelial cells), BUD:HPβCD extracted cholesterol similarly to HPβCD. On large unilamellar vesicles (LUVs), by using the fluorescent probes diphenylhexatriene (DPH) and calcein, we demonstrated an increase in membrane fluidity and permeability induced by BUD:HPβCD in vesicles containing cholesterol. On giant unilamellar vesicles (GUVs) and lipid monolayers, BUD:HPβCD induced the disruption of cholesterol-enriched raft-like liquid ordered domains as well as changes in lipid packing and lipid desorption from the cholesterol monolayers, respectively. Except for membrane fluidity, all these effects were enhanced when HPβCD was complexed with budesonide as compared with HPβCD. Since cholesterol-enriched domains have been linked to membrane signaling including pathways involved in inflammation processes, we hypothesized the effects of BUD:HPβCD could be partly mediated by changes in the biophysical properties of cholesterol-enriched domains. [less ▲]

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See detailExposure to Bacterial CpG DNA Protects from Airway Allergic Inflammation by Expanding Regulatory Lung Interstitial Macrophages.
Sabatel, Catherine ULiege; Radermecker, Coraline ULiege; Fievez, Laurence ULiege et al

in Immunity (2017), 46(3), 457-473

Living in a microbe-rich environment reduces the risk of developing asthma. Exposure of humans or mice to unmethylated CpG DNA (CpG) from bacteria reproduces these protective effects, suggesting a major ... [more ▼]

Living in a microbe-rich environment reduces the risk of developing asthma. Exposure of humans or mice to unmethylated CpG DNA (CpG) from bacteria reproduces these protective effects, suggesting a major contribution of CpG to microbe-induced asthma resistance. However, how CpG confers protection remains elusive. We found that exposure to CpG expanded regulatory lung interstitial macrophages (IMs) from monocytes infiltrating the lung or mobilized from the spleen. Trafficking of IM precursors to the lung was independent of CCR2, a chemokine receptor required for monocyte mobilization from the bone marrow. Using a mouse model of allergic airway inflammation, we found that adoptive transfer of IMs isolated from CpG-treated mice recapitulated the protective effects of CpG when administered before allergen sensitization or challenge. IM-mediated protection was dependent on IL-10, given that Il10-/- CpG-induced IMs lacked regulatory effects. Thus, the expansion of regulatory lung IMs upon exposure to CpG might underlie the reduced risk of asthma development associated with a microbe-rich environment. [less ▲]

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See detailProtean proteases: at the cutting edge of lung diseases.
Taggart, Clifford; Mall, Marcus A.; Lalmanach, Gilles et al

in European Respiratory Journal (2017), 49(2),

Proteases were traditionally viewed as mere protein-degrading enzymes with a very restricted spectrum of substrates. A major expansion in protease research has uncovered a variety of novel substrates, and ... [more ▼]

Proteases were traditionally viewed as mere protein-degrading enzymes with a very restricted spectrum of substrates. A major expansion in protease research has uncovered a variety of novel substrates, and it is now evident that proteases are critical pleiotropic actors orchestrating pathophysiological processes. Recent findings evidenced that the net proteolytic activity also relies upon interconnections between different protease and protease inhibitor families in the protease web.In this review, we provide an overview of these novel concepts with a particular focus on pulmonary pathophysiology. We describe the emerging roles of several protease families including cysteine and serine proteases.The complexity of the protease web is exemplified in the light of multidimensional regulation of serine protease activity by matrix metalloproteases through cognate serine protease inhibitor processing. Finally, we will highlight how deregulated protease activity during pulmonary pathogenesis may be exploited for diagnosis/prognosis purposes, and utilised as a therapeutic tool using nanotechnologies.Considering proteases as part of an integrative biology perspective may pave the way for the development of new therapeutic targets to treat pulmonary diseases related to intrinsic protease deregulation. [less ▲]

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See detailA Belgian survey on the diagnosis of asthma-COPD overlap syndrome.
Cataldo, Didier ULiege; Corhay, Jean-Louis ULiege; Derom, Eric et al

in International Journal of Chronic Obstructive Pulmonary Disease (2017), 12

INTRODUCTION: Patients with chronic airway disease may present features of both asthma and COPD, commonly referred to as asthma-COPD overlap syndrome (ACOS). Recommendations on their diagnosis are diffuse ... [more ▼]

INTRODUCTION: Patients with chronic airway disease may present features of both asthma and COPD, commonly referred to as asthma-COPD overlap syndrome (ACOS). Recommendations on their diagnosis are diffuse and inconsistent. This survey aimed to identify consensus on criteria for diagnosing ACOS. METHODS: A Belgian expert panel developed a survey on ACOS diagnosis, which was completed by 87 pulmonologists. Answers chosen by >/=70% of survey respondents were considered as useful criteria for ACOS diagnosis. The two most frequently selected answers were considered as major criteria, others as minor criteria. The expert panel proposed a minimal requirement of two major criteria and one minor criterion for ACOS diagnosis. Respondents were also asked which criteria are important for considering inhaled corticosteroids prescription in a COPD patient. RESULTS: To diagnose ACOS in COPD patients, major criteria were "high degree of variability in airway obstruction over time (change in forced expiratory volume in 1 second >/=400 mL)" and "high degree of response to bronchodilators (>200 mL and >/=12% predicted above baseline)". Minor criteria were "personal/family history of atopy and/or IgE sensitivity to >/=1 airborne allergen", "elevated blood/sputum eosinophil levels and/or increased fractional exhaled nitric oxide", "diagnosis of asthma <40 years of age"; "symptom variability", and "age (in favor of asthma)". To diagnose ACOS in asthma patients, major criteria were "persistence of airflow obstruction over time (forced expiratory volume in 1 second/forced vital capacity ratio <0.7)" and "exposure to noxious particles/gases, with >/=10 pack-years for (ex-)smokers"; minor criteria were "lack of response on acute bronchodilator test"; "reduced diffusion capacity"; "limited variability in airway obstruction"; "age >40 years"; "emphysema on chest computed tomography scan". CONCLUSION: Specific criteria were identified that may guide physicians to a more uniform diagnostic approach for ACOS in COPD or asthma patients. These criteria are largely similar to those used to prescribe inhaled corticosteroids in COPD. [less ▲]

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See detailDry powder of budesonide/hydroxypropyl-beta-cyclodextrin complex for inhalation as a new potential antiasthmatic treatment
Bigazzi, William ULiege; Dufour, Gilles; Mingeot-Leclercq, Marie-Paule et al

Conference (2016, October 17)

Asthma is a respiratory disease characterized by chronic airway inflammation which can lead, if not correctly managed, to tissue remodeling associated with an irreversible decline in lung function ... [more ▼]

Asthma is a respiratory disease characterized by chronic airway inflammation which can lead, if not correctly managed, to tissue remodeling associated with an irreversible decline in lung function. Hypersensitivity of the respiratory tract to non-specific stimuli, which causes triggering of asthma attacks, is also observed. Despite medical advances, asthma remains an important socio-economic and public health concern since this condition affects 300 million people and causes more than 300 000 deaths worldwide every year. Furthermore its annual cost is estimated at over 30 billion euros in Europe. These issues can be partially linked to an inadequate control of asthma due to undesirable effects of existing medication such as corticosteroids. Hence, the development of new medications with improved effectiveness and reduced adverse effects could allow a better management of the disease. It has been recently discovered that inhaled solution of hydroxylpropyl-beta-cyclodextrin (HPBCD) is able to reduce allergen-induced bronchoconstriction in asthmatic patients, with no toxicity observed in healthy patients further to administration. Based on these results, our project seeks to develop new antiasthmatic medication containing an association of HPBCD and budesonide, a widely used corticosteroid in long-term treatment of asthma. Thus, we investigated complexation between the two molecules. Interestingly, it was observed that when budesonide is complexed with HPBCD, its permeability across a Calu-3 cell layer is reduced. Several experiments in mouse models confirmed that HPBCD acts as a sustained delivery system which progressively releases budesonide into the lung parenchyma, leading to a prolonged anti-inflammatory effect. Due to high Peclet number of HPBCD, the spray dried complex exhibited wrinkled particles whose interest in dry powder for inhalation is well known. Thanks to its anti-inflammatory effect and its sustained release potential, HPBCD could significantly reduce corticosteroids needed doses for management of asthma. However, a clinical study has to be performed to determine the optimal budesonide/HPBCD ratio and the minimal effective dose of complex. Further investigations are also needed to exploit the potential of spray dried HPBCD and develop a powder for inhalation by particle engineering. [less ▲]

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See detailADAMTS3 activity is mandatory for embryonic lymphangiogenesis and regulates placental angiogenesis.
Dupont, Laura ULiege; Janssen, Lauriane; Bekhouche, Mourad et al

Conference (2016, June)

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See detailGender differences in lung tumor development : implication of estrogens
Dubois, Charline ULiege; Rocks, Natacha ULiege; CATALDO, Didier ULiege et al

Conference (2016, May 27)

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See detailGender differences in lung tumor development : implication of estrogens
Dubois, Charline ULiege; Rocks, Natacha ULiege; Cataldo, Didier ULiege et al

Conference (2016, May 11)

Detailed reference viewed: 20 (1 ULiège)
See detailInvolvement of microenvironment modulations in lung metastasis formation
Donati, Kim ULiege; Sepult, Christelle ULiege; Noël, Agnès ULiege et al

Conference (2016, May 11)

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See detailStimulated release and functional activity of surface expressed metalloproteinase ADAM17 in exosomes.
Groth, Esther; Pruessmeyer, Jessica; Babendreyer, Aaron et al

in Biochimica et Biophysica Acta (2016), 1863(11), 2795-2808

By mediating proteolytic shedding on the cell surface the disintegrin and metalloproteinases ADAM10 and ADAM17 function as critical regulators of growth factors, cytokines and adhesion molecules. We here ... [more ▼]

By mediating proteolytic shedding on the cell surface the disintegrin and metalloproteinases ADAM10 and ADAM17 function as critical regulators of growth factors, cytokines and adhesion molecules. We here report that stimulation of lung epithelial A549 tumor cells with phorbol-12-myristate-13-acetate (PMA) leads to the downregulation of the surface expressed mature form of ADAM17 without affecting ADAM10 expression. This reduction could not be sufficiently explained by metalloproteinase-mediated degradation, dynamin-mediated internalization or microdomain redistribution of ADAM17. Instead, surface downregulation of ADAM17 was correlated with the presence of its mature form in exosomes. Exosomal ADAM17 release was also observed in monocytic and primary endothelial cells where it could be induced by stimulation with lipopolysaccharide. Antibody-mediated surface labelling of ADAM17 revealed that at least part of exosomal ADAM17 was oriented with the metalloproteinase domain outside and had been expressed on the cell surface. Suppression of iRHOM2-mediated ADAM17 maturation prevented surface expression and exosomal release of ADAM17. Further, deletion of the protease's C-terminus or cell treatment with a calcium chelator diminished exosomal release as well as surface downregulation of ADAM17, underlining that both processes are closely associated. Co-incubation of ADAM17 containing exosomes with cells expressing the ADAM17 substrates TGFalpha or amphiregulin lead to increased shedding of both substrates. This was prevented when exosomes were prepared from cells with shRNA-mediated ADAM17 knockdown. These data indicate that cell stimulation can downregulate expression of mature ADAM17 from the cell surface and induce release of exosomal ADAM17, which can then distribute and contribute to substrate shedding on more distant cells. [less ▲]

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