Peptide density targets and impedes triple negative breast cancer metastasis

Authors

Daxing Liu, CUNY City College
Peng Guo, CUNY City College
Craig McCarthy, CUNY City College
Biran Wang, CUNY City College
Yu Tao, CUNY City College
Debra Auguste, CUNY City CollegeFollow

Document Type

Article

Publication Date

2018

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 threedimensional 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 DV1functionalized 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.

Comments

This article was originally published in Nature Communications, available at DOI: 10.1038/s41467-018-05035-5.

This article is licensed under a Creative Commons Attribution 4.0 International License.