title: Activated α2-Macroglobulin Induces Mesenchymal Cellular Migration Of Raw264.7 Cells Through Low-Density Lipoprotein Receptor-Related Protein 1.
abstract: Distinct modes of cell migration contribute to diverse types of cell movements. The mesenchymal mode is characterized by a multistep cycle of membrane protrusion, the formation of focal adhesion, and the stabilization at the leading edge associated with the degradation of extracellular matrix (ECM) components and with regulated extracellular proteolysis. Both α2-Macroglobulin (α2M) and its receptor, low density lipoprotein receptor-related protein 1 (LRP1), play important roles in inflammatory processes, by controlling the extracellular activity of several proteases. The binding of the active form of α2M (α2M*) to LRP1 can also activate different signaling pathways in macrophages, thus inducing extracellular matrix metalloproteinase-9 (MMP-9) activation and cellular proliferation. In the present study, we investigated whether the α2M*/LRP1 interaction induces cellular migration of the macrophage-derived cell line, Raw264.7. By using the wound-scratch migration assay and confocal microscopy, we demonstrate that α2M* induces LRP1-mediated mesenchymal cellular migration. This migration exhibits the production of enlarged cellular protrusions, MT1-MMP distribution to these leading edge protrusions, actin polymerization, focal adhesion formation, and increased intracellular LRP1/β1-integrin colocalization. Moreover, the presence of calphostin-C blocked the α2M*-stimulated cellular protrusions, suggesting that the PKC activation is involved in the cellular motility of Raw264.7 cells. These findings could constitute a therapeutic target for inflammatory processes with deleterious consequences for human health, such as rheumatoid arthritis, atherosclerosis and cancer. J. Cell. Biochem. 118: 1810-1818, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Ciudad Universitaria (5000), Córdoba, Argentina.
authors.forename: Darío G
authors.initials: DG
authors.lastname: Ferrer
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Ciudad Universitaria (5000), Córdoba, Argentina.
authors.forename: Virginia Actis
authors.initials: VA
authors.lastname: Dato
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Ciudad Universitaria (5000), Córdoba, Argentina.
authors.forename: Javier R
authors.initials: JR
authors.lastname: Jaldín-Fincati
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Ciudad Universitaria (5000), Córdoba, Argentina.
authors.forename: Valeria E
authors.initials: VE
authors.lastname: Lorenc
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Ciudad Universitaria (5000), Córdoba, Argentina.
authors.forename: María C
authors.initials: MC
authors.lastname: Sánchez
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Ciudad Universitaria (5000), Córdoba, Argentina.
authors.forename: Gustavo A
authors.identifier: 0000-0001-8902-6693
authors.initials: GA
authors.lastname: Chiabrando
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D009281:Naphthalenes / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects; D000511:alpha-Macroglobulins / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D009281:Naphthalenes; D000511:alpha-Macroglobulins; D011493:Protein Kinase C; D020780:Matrix Metalloproteinase 9; C058819:calphostin C
keywords: ENDOCYTOSIS; LDL RECEPTORS; MIGRATION; α-MACROGLOBULINS