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

Alexia Arpel (1, 2) , Coralie Gamper (1) , Caroline Spenlé (1) , Aurore Fernandez (1) , Laurent Jacob (1) , Nadège Baumlin (1) , Patrice Laquerriere (2) , Gertraud Orend (1) , Gérard Crémel (1) , Dominique Bagnard (1)

1 IRM - Immuno-Rhumatologie Moléculaire
2 IPHC - Institut Pluridisciplinaire Hubert Curien

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.

Domaines: Physique [physics]

Alexia Arpel, Coralie Gamper, Caroline Spenlé, Aurore Fernandez, Laurent Jacob, et al.. Inhibition of primary breast tumor growth and metastasis using a neuropilin-1 transmembrane domain interfering peptide. Oncotarget, 2016, 7 (34), ⟨10.18632/oncotarget.10101⟩. ⟨hal-01412954⟩