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Activated α 2 ‐Macroglobulin Induces Mesenchymal Cellular Migration Of Raw264.7 Cells Through Low‐Density Lipoprotein Receptor‐Related Protein 1
Author(s) -
Ferrer Darío G.,
Dato Virginia Actis,
JaldínFincati Javier R.,
Lorenc Valeria E.,
Sánchez María C.,
Chiabrando Gustavo A.
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25857
Subject(s) - lrp1 , microbiology and biotechnology , cell migration , extracellular matrix , focal adhesion , chemistry , extracellular , lamellipodium , cell adhesion , biology , signal transduction , ldl receptor , cell , biochemistry , lipoprotein , cholesterol
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 α 2 ‐Macroglobulin (α 2 M) 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 α 2 M (α 2 M*) 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 α 2 M*/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 α 2 M* 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 α 2 M*‐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.