title: Pleiotrophin exerts its migration and invasion effect through the neuropilin-1 pathway.
abstract: Pleiotrophin (PTN) is a pleiotropic growth factor that exhibits angiogenic properties and is involved in tumor growth and metastasis. Although it has been shown that PTN is expressed in tumor cells, few studies have investigated its receptors and their involvement in cell migration and invasion. Neuropilin-1 (NRP-1) is a receptor for multiple growth factors that mediates cell motility and plays an important role in angiogenesis and tumor progression. Here we provide evidence for the first time that NRP-1 is crucial for biological activities of PTN. We found that PTN interacted directly with NRP-1 through its thrombospondin type-I repeat domains. Importantly, binding of PTN to NRP-1 stimulated the internalization and recycling of NRP-1 at the cell surface. Invalidation of NRP-1 by RNA interference in human carcinoma cells inhibited PTN-induced intracellular signaling of the serine-threonine kinase, mitogen-activated protein MAP kinase, and focal adhesion kinase pathways. Accordingly, NRP-1 silencing or blocking by antibody inhibited PTN-induced human umbilical vein endothelial cell migration and tumor cell invasion. These results suggest that NRP-1/PTN interaction provides a novel mechanism for controlling the response of endothelial and tumoral cells to PTN and may explain, at least in part, how PTN contributes to tumor angiogenesis and cancer progression.
authors.affiliation: Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires (CRRET), CNRS; Université Paris-Est Créteil, France.
authors.forename: Rania
authors.initials: R
authors.lastname: Elahouel
authors.affiliation: INSERM, U955, Equipe 7, 94000 Créteil, France; Université Paris-Est, Faculté de médecine, 94000 Créteil, France.
authors.forename: Charly
authors.initials: C
authors.lastname: Blanc
authors.affiliation: Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires (CRRET), CNRS; Université Paris-Est Créteil, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Carpentier
authors.affiliation: Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires (CRRET), CNRS; Université Paris-Est Créteil, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Frechault
authors.affiliation: Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires (CRRET), CNRS; Université Paris-Est Créteil, France.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cascone
authors.affiliation: Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires (CRRET), CNRS; Université Paris-Est Créteil, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Destouches
authors.affiliation: Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires (CRRET), CNRS; Université Paris-Est Créteil, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Delbé
authors.affiliation: Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires (CRRET), CNRS; Université Paris-Est Créteil, France.
authors.forename: José
authors.initials: J
authors.lastname: Courty
authors.affiliation: Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires (CRRET), CNRS; Université Paris-Est Créteil, France. Electronic address: Yamina.HAMMA@inserm.fr.
authors.forename: Yamina
authors.initials: Y
authors.lastname: Hamma-Kourbali
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D011993:Recombinant Fusion Proteins; C066845:pleiotrophin; D039942:Neuropilin-1; D005982:Glutathione Transferase