Inhibition of primary breast tumor growth and metastasis using a neuropilin-1 transmembrane domain interfering peptide

// Alexia Arpel 1, 2 , Coralie Gamper 1 , Caroline Spenle 1 , Aurore Fernandez 1 , Laurent Jacob 1 , Nadege Baumlin 1 , Patrice Laquerriere 2 , Gertraud Orend 1 , Gerard Cremel 1 , Dominique Bagnard 1 1 INSERM U 1109, MN3T Laboratory, Labex Medalis, Strasbourg University, Strasbourg, France 2 CNRS UMR 7178, Institut Pluridisciplinaire Hubert Curien, Strasbourg University, Strasbourg, France Correspondence to: Dominique Bagnard, email: bagnard@unistra.fr Keywords: neuropilin-1, breast cancer, metastasis, treatment, peptide Received: September 28, 2015     Accepted: May 28, 2016     Published: June 16, 2016 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.