title: Inhibition of primary breast tumor growth and metastasis using a neuropilin-1 transmembrane domain interfering peptide.
abstract: The transmembrane domains (TMD) in membrane receptors play a key role in cell signaling. As previously shown by us a peptide targeting the TMD of neuropilin-1 (MTP-NRP1), blocks cell proliferation, cell migration and angiogenesis in vitro, and decreases glioblastoma growth in vivo. We now explored the clinical potential of MTP-NRP1 on breast cancer models and demonstrate that MTP-NRP1 blocks proliferation of several breast cancer lines including the MDA-MB-231, a triple negative human breast cancer cell line. In models with long term in vivo administration of the peptide, MTP-NRP1 not only reduced tumor volume but also decreased number and size of breast cancer metastases. Strikingly, treating mice before tumors developed protected from metastasis establishment/formation. Overall, our results report that targeting the TMD of NRP1 in breast cancer is a potent new strategy to fight against breast cancer and related metastasis.
authors.affiliation: INSERM U 1109, MN3T Laboratory, Labex Medalis, Strasbourg University, Strasbourg, France.|CNRS UMR 7178, Institut Pluridisciplinaire Hubert Curien, Strasbourg University, Strasbourg, France.
authors.forename: Alexia
authors.initials: A
authors.lastname: Arpel
authors.affiliation: INSERM U 1109, MN3T Laboratory, Labex Medalis, Strasbourg University, Strasbourg, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Gamper
authors.affiliation: INSERM U 1109, MN3T Laboratory, Labex Medalis, Strasbourg University, Strasbourg, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Spenlé
authors.affiliation: INSERM U 1109, MN3T Laboratory, Labex Medalis, Strasbourg University, Strasbourg, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Fernandez
authors.affiliation: INSERM U 1109, MN3T Laboratory, Labex Medalis, Strasbourg University, Strasbourg, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Jacob
authors.affiliation: INSERM U 1109, MN3T Laboratory, Labex Medalis, Strasbourg University, Strasbourg, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Baumlin
authors.affiliation: CNRS UMR 7178, Institut Pluridisciplinaire Hubert Curien, Strasbourg University, Strasbourg, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Laquerriere
authors.affiliation: INSERM U 1109, MN3T Laboratory, Labex Medalis, Strasbourg University, Strasbourg, France.
authors.forename: Gertraud
authors.initials: G
authors.lastname: Orend
authors.affiliation: INSERM U 1109, MN3T Laboratory, Labex Medalis, Strasbourg University, Strasbourg, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Crémel
authors.affiliation: INSERM U 1109, MN3T Laboratory, Labex Medalis, Strasbourg University, Strasbourg, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bagnard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D061986:MCF-7 Cells; D051379:Mice; D009362:Neoplasm Metastasis; D039942:Neuropilin-1 / Q000737:chemistry*; D010455:Peptides / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D010455:Peptides; D039942:Neuropilin-1
keywords: breast cancer; metastasis; neuropilin-1; peptide; treatment