2. Academic Validation
  3. Peptide density targets and impedes triple negative breast cancer metastasis

Peptide density targets and impedes triple negative breast cancer metastasis

  • Nat Commun. 2018 Jul 4;9(1):2612. doi: 10.1038/s41467-018-05035-5.
Daxing Liu 1 2,  Peng Guo 1 3 4,  Craig McCarthy 1,  Biran Wang 1,  Yu Tao 1,  Debra Auguste 5 6
Affiliations

Affiliations

  • 1 Department of Biomedical Engineering, The City College of New York. New York, NY, 10031, USA.
  • 2 Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA, 02115, USA.
  • 3 Vascular Biology Program, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
  • 4 Department of Surgery, Harvard Medical School and Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
  • 5 Department of Biomedical Engineering, The City College of New York. New York, NY, 10031, USA. [email protected].
  • 6 Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA, 02115, USA. [email protected].
PMID: 29973594 DOI: 10.1038/s41467-018-05035-5
Abstract

The C-X-C Chemokine Receptor type 4 (CXCR4, CD184) pathway is a key regulator of Cancer metastasis. Existing therapeutics that block CXCR4 signaling are dependent on single molecule-receptor interactions or silencing CXCR4 expression. CXCR4 localizes in lipid rafts and forms dimers therefore CXCR4 targeting and signaling may depend on ligand density. Herein, we report liposomes presenting a CXCR4 binding peptide (DV1) as a three-dimensional molecular array, ranging from 9k to 74k molecules μm-2, target triple negative breast Cancer (TNBC). TNBC cells exhibit a maxima in binding and uptake of DV1-functionalized liposomes (L-DV1) in vitro at a specific density, which yields a significant reduction in cell migration. This density inhibits metastasis from a primary tumor for 27 days, resulting from peptide density dependent gene regulation. We show that complementing cell membrane receptor expression may be a strategy for targeting cells and regulating signaling.

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