Peptide density targets and impedes triple negative breast cancer metastasis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29973594.
- Also identified by DOI 10.1038/s41467-018-05035-5 and PMC identifier 6031661.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-2</sup>, 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.
Medical subject headings
- Antineoplastic Agents
- Brain Neoplasms
- Liver Neoplasms
- Lung Neoplasms
- Peptides
- Receptors, CXCR4
- Triple Negative Breast Neoplasms