title: Role of LRP-1 in cancer cell migration in 3-dimensional collagen matrix.
abstract: The low-density lipoprotein receptor-related protein-1 (LRP-1) is a member of Low Density Lipoprotein Receptor (LDLR) family, which is ubiquitously expressed and which is described as a multifunctional endocytic receptor which mediates the clearance of various extracellular matrix molecules including serine proteinases, proteinase-inhibitor complexes, and matricellular proteins. Several studies showed that high LRP-1 expression promotes breast cancer cell invasiveness, and LRP-1 invalidation leads to cell motility abrogation in both tumor and non-tumor cells. Furthermore, our group has reported that LRP-1 silencing prevents the invasion of a follicular thyroid carcinoma despite increased pericellular proteolytic activities from MMP2 and uPA using a 2D-cell culture model. As the use of 3D culture systems is becoming more and more popular due to their promise as enhanced models of tissue physiology, the aim of the present work is to characterize for the first time how the 3D collagen type I matrix may impact the ability of LRP-1 to regulate the migratory properties of thyroid carcinoma using as a model FTC-133 cells. Our results show that inhibition of LRP-1 activity or expression leads to morphological changes affecting cell-matrix interactions, reorganizations of the actin-cytoskeleton especially by inhibiting FAK activation and increasing RhoA activity and MLC-2 phosphorylation, thus preventing cell migration. Taken together, our results suggest that LRP-1 silencing leads to a decrease of cell migratory capacity in a 3D configuration.
authors.affiliation: a Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7369 Matrice Extracellulaire et Dynamique Cellulaire, Université de Reims Champagne-Ardenne, Unité de Formation et de Recherche Sciences Exactes et Naturelles , Reims , France.
authors.forename: Aline
authors.initials: A
authors.lastname: Appert-Collin
authors.affiliation: a Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7369 Matrice Extracellulaire et Dynamique Cellulaire, Université de Reims Champagne-Ardenne, Unité de Formation et de Recherche Sciences Exactes et Naturelles , Reims , France.|b UMR CNRS 7360, LIEC, Université de Lorraine , Metz , France.
authors.forename: Amar
authors.initials: A
authors.lastname: Bennasroune
authors.affiliation: c Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7369 Matrice Extracellulaire et Dynamique Cellulaire, Université de Reims Champagne-Ardenne, Faculté de Pharmacie , Reims , France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Jeannesson
authors.affiliation: d Plateforme d'Imagerie Cellulaire et Tissulaire, URCA , Reims , France.
authors.forename: Christine
authors.initials: C
authors.lastname: Terryn
authors.affiliation: e UMR 7213 CNRS, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie , Illkirch , France.
authors.forename: Guy
authors.initials: G
authors.lastname: Fuhrmann
authors.affiliation: c Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7369 Matrice Extracellulaire et Dynamique Cellulaire, Université de Reims Champagne-Ardenne, Faculté de Pharmacie , Reims , France.
authors.forename: Hamid
authors.initials: H
authors.lastname: Morjani
authors.affiliation: a Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7369 Matrice Extracellulaire et Dynamique Cellulaire, Université de Reims Champagne-Ardenne, Unité de Formation et de Recherche Sciences Exactes et Naturelles , Reims , France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dedieu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D026563:LDL-Receptor Related Protein-Associated Protein / Q000494:pharmacology; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D015203:Reproducibility of Results; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D026563:LDL-Receptor Related Protein-Associated Protein; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D018994:Myosin Light Chains; D011994:Recombinant Proteins; D003094:Collagen; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: 3D matrix; FTC-133 cells; LRP-1; collagen type I; migration