Search

Your search keyword '"Caroline Roelants"' showing total 5 results
Start Over Author "Caroline Roelants" Topic medicine.anatomical_structure
5 results on '"Caroline Roelants"'

1. Different cardiovascular and pulmonary phenotypes for single- and double-knock-out mice deficient in BMP9 and BMP10

Author

Nihel Berrebeh, Emmanuelle Tillet, Hequn Liu, Christophe Guignabert, Ly Tu, Sabine Bailly, Christophe Battail, Martina Rossi, Nicolas Chaumontel, Marie Ouarné, Laurent Savale, Thomas Daubon, Marc Humbert, Agnès Desroches-Castan, Christine Mallet, Caroline Roelants, Elise Helfer, Claire Bouvard, Pascale Perret, Andreas Bikfalvi, Bailly, Sabine, Famille BMP dans l'angiogenèse et la lymphangiogenèse (BAL), BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Université Paris-Saclay, Invasion mechanisms in angiogenesis and cancer (IMAC), CEA- Saclay (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Adhésion et Inflammation (LAI), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Chirurgical Marie Lannelongue (CCML), Inovarion, Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Radiopharmaceutiques biocliniques (LRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), ANR-17-CE14-0006,B9inPAH,BMP9 un modulateur clef du tonus vasculaire dans l'hypertension artérielle pulmonaire : une nouvelle cible thérapeutique à haut potentiel(2017), ANR-15-IDEX-0002,UGA,IDEX UGA(2015), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-11-INBS-0006,FLI,France Life Imaging(2011), European Project: EQU202003010188,V.A.Cure-814316, DAUBON, Thomas, BMP9 un modulateur clef du tonus vasculaire dans l'hypertension artérielle pulmonaire : une nouvelle cible thérapeutique à haut potentiel - - B9inPAH2017 - ANR-17-CE14-0006 - AAPG2017 - VALID, IDEX UGA - - UGA2015 - ANR-15-IDEX-0002 - IDEX - VALID, CBH-EUR-GS - - CBH-EUR-GS2017 - ANR-17-EURE-0003 - EURE - VALID, Infrastructures - France Life Imaging - - FLI2011 - ANR-11-INBS-0006 - INBS - VALID, H2020 MarieSkłodowska-Curie Actions - V.A.Cure-814316 - EQU202003010188 - INCOMING, Famille BMP dans l'angiogenèse et la lymphangiogenèse (BAL ), Biologie du Cancer et de l'Infection (BCI ), Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre chirurgical Marie Lannelongue, and Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, medicine.medical_specialty, Physiology, Activin Receptors, Type II, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Pathogenesis, Mice, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), Internal medicine, pulmonary hypertension, Growth Differentiation Factor 2, medicine, bone morphogenetic proteins, Animals, Hypoxia, Lung, Mice, Knockout, Endothelin receptor antagonist, business.industry, medicine.disease, Pulmonary hypertension, Bosentan, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV] Life Sciences [q-bio], vascular anomalies, Phenotype, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, high-output heart failure, Heart failure, Knockout mouse, Vascular resistance, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Vasoconstriction, pulmonary vascular remodeling, medicine.drug
Abstract

Aims BMP9 and BMP10 mutations were recently identified in patients with pulmonary arterial hypertension, but their specific roles in the pathogenesis of the disease are still unclear. We aimed to study the roles of BMP9 and BMP10 in cardiovascular homeostasis and pulmonary hypertension using transgenic mouse models deficient in Bmp9 and/or Bmp10. Methods and results Single- and double-knockout mice for Bmp9 (constitutive) and/or Bmp10 (tamoxifen inducible) were generated. Single-knock-out (KO) mice developed no obvious age-dependent phenotype when compared with their wild-type littermates. However, combined deficiency in Bmp9 and Bmp10 led to vascular defects resulting in a decrease in peripheral vascular resistance and blood pressure and the progressive development of high-output heart failure and pulmonary hemosiderosis. RNAseq analysis of the lungs of the double-KO mice revealed differential expression of genes involved in inflammation and vascular homeostasis. We next challenged these mice to chronic hypoxia. After 3 weeks of hypoxic exposure, Bmp10-cKO mice showed an enlarged heart. However, although genetic deletion of Bmp9 in the single- and double-KO mice attenuated the muscularization of pulmonary arterioles induced by chronic hypoxia, we observed no differences in Bmp10-cKO mice. Consistent with these results, endothelin-1 levels were significantly reduced in Bmp9 deficient mice but not Bmp10-cKO mice. Furthermore, the effects of BMP9 on vasoconstriction were inhibited by bosentan, an endothelin receptor antagonist, in a chick chorioallantoic membrane assay. Conclusions Our data show redundant roles for BMP9 and BMP10 in cardiovascular homeostasis under normoxic conditions (only combined deletion of both Bmp9 and Bmp10 was associated with severe defects) but highlight specific roles under chronic hypoxic conditions. We obtained evidence that BMP9 contributes to chronic hypoxia-induced pulmonary vascular remodelling, whereas BMP10 plays a role in hypoxia-induced cardiac remodelling in mice.

Published
2021

2. Protein kinase CK2 contributes to placental development: physiological and pathological implications

Author

Nicolas Lemaitre, Claude Cochet, Daniel Vaiman, Déborah Reynaud, Odile Filhol, Mohamed Benharouga, Nadia Alfaidy, Roland Abi Nahed, Solene Lartigue, Caroline Roelants, Invasion mechanisms in angiogenesis and cancer (IMAC), Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Inovarion, Inovarion [Paris], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie des Métaux (BioMet), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Biologie des Métaux (BioMet ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Invasion de trophoblastes, Modèle animal, Prééclampsie, Adolescent, Protein subunit, Placenta, Biology, Preeclampsia, Andrology, Mice, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pre-Eclampsia, Pregnancy, In vivo, Cell Line, Tumor, Drug Discovery, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, Casein Kinase II, Genetics (clinical), reproductive and urinary physiology, Trophoblast, medicine.disease, Molecular medicine, Placentation, In vitro, Trophoblasts, Mice, Inbred C57BL, Disease Models, Animal, Pregnancy Trimester, First, Protéine kinase CK2, medicine.anatomical_structure, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, embryonic structures, Molecular Medicine, Female, Ex vivo, 030215 immunology
Abstract

International audience; Preeclampsia (PE) is the most threatening pathology of human pregnancy. Its development is thought to be due to a failure in the invasion of trophoblast cells that establish the feto-maternal circulation. Protein kinase CK2 is a ubiquitous enzyme reported to be involved in the control of cell invasion. CK2 consists of two subunits, a catalytic subunit, CK2α, and a regulatory subunit, CK2β. To date, no data exist regarding the expression and role of this enzyme in normal and PE pregnancies. We performed studies, at the clinical level using distinctive cohorts from early pregnancy (n = 24) and from PE (n = 23) and age-matched controls (n = 28); in vitro, using trophoblast cell lines; ex vivo, using placental explants; and in vivo, using PE mouse models. We demonstrated that (i) CK2 is more expressed during the late first trimester of pregnancy and is mainly localized in differentiated trophoblast cells, (ii) the inhibition of its enzymatic activity decreased the proliferation, migration, invasion, and syncytialization of trophoblast cells, both in 2D and 3D culture systems, and (iii) CK2 activity and the CK2α/CK2β protein ratio were increased in PE human placentas. The pattern and profile of CK2 expression were confirmed in gravid mice along with an increase in the PE mouse models. Altogether, our results demonstrate that CK2 plays an essential role in the establishment of the feto-maternal circulation and that its deregulation is associated with PE development. The increase in CK2 activity in PE might constitute a compensatory mechanism to ensure proper pregnancy progress.

Published
2020

3. The size-speed-force relationship governs migratory cell response to tumorigenic factors

Author

Andreas Christ, Aldo Leal-Egaña, Timothée Vignaud, Caroline Roelants, Gaëlle Letort, Manuel Théry, Odile Filhol, Jean Louis Martiel, Physiologie cellulaire et végétale (LPCV), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Invasion mechanisms in angiogenesis and cancer (IMAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Alloimmunité-Autoimmunité-Transplantation (A2T), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Institut National du Cancer (INCA PLBIO2011), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National du Cancer [INCA PLBIO2011], Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)

Subjects
0301 basic medicine, Cell contractility, Carcinogenesis, Receptor, ErbB-2, Cell, Tumorigenic factors, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Contractile Proteins, Cell Movement, Transforming Growth Factor beta, Tumor development, ComputingMilieux_MISCELLANEOUS, Cancer, education.field_of_study, Human breast cell, Cell migration, Anatomy, Cell mechanics, Articles, Cell biology, Biomechanical Phenomena, Cell Motility, medicine.anatomical_structure, Cell Transformation, Neoplastic, Female, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Collagen Type I, Contractility, 03 medical and health sciences, Cell Line, Tumor, medicine, Cell Adhesion, Humans, education, Molecular Biology, Cell Proliferation, Cell Size, Cell growth, Cell Biology, Traction forces, Fibronectin, 030104 developmental biology, Cell culture, biology.protein, Transforming growth factor
Abstract

Normal and transformed motile cells follow a common trend in which size and contractile forces are negatively correlated with cell speed. However, tumorigenic factors amplify the preexisting population heterogeneity and lead some cells to exhibit biomechanical properties that are more extreme than those observed with normal cells., Tumor development progresses through a complex path of biomechanical changes leading first to cell growth and contraction and then cell deadhesion, scattering, and invasion. Tumorigenic factors may act specifically on one of these steps or have a wider spectrum of actions, leading to a variety of effects and thus sometimes to apparent contradictory outcomes. Here we used micropatterned lines of collagen type I/fibronectin on deformable surfaces to standardize cell behavior and measure simultaneously cell size, speed of motion and magnitude of the associated traction forces at the level of a single cell. We analyzed and compared the normal human breast cell line MCF10A in control conditions and in response to various tumorigenic factors. In all conditions, a wide range of biomechanical properties was identified. Despite this heterogeneity, normal and transformed motile cells followed a common trend whereby size and contractile forces were negatively correlated with cell speed. Some tumorigenic factors, such as activation of ErbB2 or loss of the βsubunit of casein kinase 2, shifted the whole population toward a faster speed and lower contractility state. Treatment with transforming growth factor β induced some cells to adopt opposing behaviors such as extremely high versus extremely low contractility. Thus tumor transformation amplified preexisting population heterogeneity and led some cells to exhibit biomechanical properties that were more extreme than those observed with normal cells.

Published
2017

4. The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma

Author

Helena Polena, Ellen Blanc, Abir Khalil-Mgharbel, Delphine Borchiellini, Gilles Pagès, Jean-Marc Ferrero, Maeva Dufies, Isabelle Vilgrain, Céline Ferlay-Segura, Aude Salomon, Alban Deroux, Odile Filhol, Adama Sidibé, Jean-Louis Quesada, Sylvie Negrier, Julie Creuzet, Bernard Escudier, Caroline Roelants, Claude Cochet, Biologie du Cancer et de l'Infection (BCI ), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Université Grenoble Alpes - Institut d'Administration des Entreprises (UGA IAE), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Invasion mechanisms in angiogenesis and cancer (IMAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Université Grenoble Alpes - UFR Médecine (UGA UFRM), CIC - Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Délégation à la Recherche Clinique et à l'Innovation [Lyon] (DRCI), UNICANCER - Centre Léon Bérard Lyon (Rhône)-Centre de Lutte Contre le Cancer de Lyon et Rhône-Alpes, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Oncologie génito-urinaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Université de Lyon, Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Angiogenèse hormono-regulée et angiogenèse tumorale (LAPV), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Transduction du signal : signalisation calcium, phosphorylation et inflammation, Centre Léon Bérard [Lyon], Laboratoire de Probabilités, Statistiques et Modélisations (LPSM (UMR_8001)), Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Centre Léon Bérard [Lyon]-UNICANCER - Centre Léon Bérard Lyon (Rhône), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)

Subjects
0301 basic medicine, Cancer Research, Bevacizumab, Endothelium, medicine.drug_class, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Tyrosine-kinase inhibitor, Biomarkers, Pharmacological, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Biomarkers, Tumor, Human Umbilical Vein Endothelial Cells, Sunitinib, Humans, Molecular Targeted Therapy, Neoplasm Metastasis, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Carcinoma, Renal Cell, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Clinical Trials as Topic, business.industry, medicine.disease, Cadherins, Metastatic breast cancer, Kidney Neoplasms, 3. Good health, Endothelial stem cell, 030104 developmental biology, medicine.anatomical_structure, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Cancer research, Endothelium, Vascular, VE-cadherin, business, Kidney cancer, medicine.drug
Abstract

Background Vascular endothelial (VE)-cadherin is an endothelial cell-specific protein responsible for endothelium integrity. Its adhesive properties are regulated by post-translational processing, such as tyrosine phosphorylation at site Y685 in its cytoplasmic domain, and cleavage of its extracellular domain (sVE). In hormone-refractory metastatic breast cancer, we recently demonstrated that sVE levels correlate to poor survival. In the present study, we determine whether kidney cancer therapies had an effect on VE-cadherin structural modifications and their clinical interest to monitor patient outcome. Methods The effects of kidney cancer biotherapies were tested on an endothelial monolayer model mimicking the endothelium lining blood vessels and on a homotypic and heterotypic 3D cell model mimicking tumour growth. sVE was quantified by ELISA in renal cell carcinoma patients initiating sunitinib (48 patients) or bevacizumab (83 patients) in the first-line metastatic setting (SUVEGIL and TORAVA trials). Results Human VE-cadherin is a direct target for sunitinib which inhibits its VEGF-induced phosphorylation and cleavage on endothelial monolayer and endothelial cell migration in the 3D model. The tumour cell environment modulates VE-cadherin functions through MMPs and VEGF. We demonstrate the presence of soluble VE-cadherin in the sera of mRCC patients (n = 131) which level at baseline, is higher than in a healthy donor group (n = 96). Analysis of sVE level after 4 weeks of treatment showed that a decrease in sVE level discriminates the responders vs. non-responders to sunitinib, but not bevacizumab. Conclusions These data highlight the interest for the sVE bioassay in future follow-up of cancer patients treated with targeted therapies such as tyrosine-kinase inhibitors.

Published
2018

5. Heterogeneity of single-cell mechanical responses to tumorigenic factors

Author

Manuel Théry, Jean-Louis Martiel, Aldo Leal-Egaña, Odile Filhol, Andreas Christ, Timothée Vignaud, Caroline Roelants, and Gaëlle Letort

Subjects
0303 health sciences, education.field_of_study, biology, Cell growth, Population, Cell, Transforming growth factor beta, Anatomy, Cell biology, Fibronectin, Contractility, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Cell culture, 030220 oncology & carcinogenesis, medicine, biology.protein, Casein kinase 2, education, 030304 developmental biology
Abstract

Tumor development progresses through a complex path of biomechanical changes leading first to cell growth and contraction followed by cell de-adhesion, scattering and invasion. Tumorigenic factors may act specifically on one of these steps or have wider spectrum of actions, leading to a variety of effects and thus sometimes to apparent contradictory outcomes. Here we used micropatterned lines of collagen type-I/fibronectin on deformable surfaces to standardize cell behavior and to measure simultaneously cell size, speed of motion and the magnitude of the associated contractile forces at the level of a single cell. We analyzed and compared normal human breast cell line MCF10A in control conditions and in response to various tumorigenic factors. In all conditions, distinct populations of cells with a wide range of biomechanical properties were identified. Despite this heterogeneity, normal and transformed motile cells followed a common trend whereby size and contractile forces were negatively correlated with cell speed. Some tumorigenic factors, such as activation of ErbB2 or the loss of the beta subunit of casein kinase 2 (CK2), shifted the whole population towards a faster speed and lower contractility state. Treatment with transforming growth factor beta (TGF-β), induced some cells to adopt opposing behaviors such as extreme high contractility versus extreme low contractility. Thus, tumor transformation amplified the pre-existing population heterogeneity and led some cells to exhibit biomechanical properties that were more extreme than that observed with normal cells.

Published
2016

Catalog

Books, media, physical & digital resources
See catalog results