Inhibition of primary breast tumor growth and metastasis using a neuropilin-1 transmembrane domain interfering peptide
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Alexia Arpel1,2, Coralie Gamper1, Caroline Spenlé1, Aurore Fernandez1, Laurent Jacob1, Nadège Baumlin1, Patrice Laquerriere2, Gertraud Orend1, Gérard Crémel1, Dominique Bagnard1
1INSERM U 1109, MN3T Laboratory, Labex Medalis, Strasbourg University, Strasbourg, France
2CNRS UMR 7178, Institut Pluridisciplinaire Hubert Curien, Strasbourg University, Strasbourg, France
Dominique Bagnard, email: [email protected]
Keywords: neuropilin-1, breast cancer, metastasis, treatment, peptide
Received: September 28, 2015 Accepted: May 28, 2016 Published: June 16, 2016
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.
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