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

Oncotarget. 2016 Aug 23;7(34):54723-54732. doi: 10.18632/oncotarget.10101.

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.

Keywords: breast cancer; metastasis; neuropilin-1; peptide; treatment.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • HEK293 Cells
  • Humans
  • Kaplan-Meier Estimate
  • MCF-7 Cells
  • Mice
  • Neoplasm Metastasis
  • Neuropilin-1 / chemistry*
  • Peptides / pharmacology*
  • Tumor Burden / drug effects*
  • Xenograft Model Antitumor Assays*

Substances

  • Peptides
  • Neuropilin-1