ICAM-1 as a molecular target for triple negative breast cancer

Proc Natl Acad Sci U S A. 2014 Oct 14;111(41):14710-5. doi: 10.1073/pnas.1408556111. Epub 2014 Sep 29.

Abstract

Triple negative breast cancers (TNBCs) have a high mortality rate owing to aggressive proliferation and metastasis and a lack of effective therapeutic options. Herein, we describe the overexpression of intercellular adhesion molecule-1 (ICAM-1) in human TNBC cell lines and tissues, and demonstrate that ICAM-1 is a potential molecular target and biomarker for TNBC therapy and diagnosis. We synthesized ICAM-1 antibody-conjugated iron oxide nanoparticles (ICAM-IONPs) as a magnetic resonance imaging (MRI) probe to evaluate tumor targeting. Quantitative analysis of ICAM-1 surface expression predicted the targeting capability of ICAM-IONPs to TNBC cells. MRI of the TNBC xenograft tumor after systemic administration of ICAM-IONPs, coupled with iron quantification and histology, demonstrated a significant and sustained MRI contrast enhancement and probe accumulation in tumors with ICAM-1 overexpression relative to control. Identification of ICAM-1 as a TNBC target and biomarker may lead to the development of a new strategy and platform for addressing a critical gap in TNBC patient care.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Female
  • Ferric Compounds / chemistry
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Magnetic Resonance Imaging
  • Mice
  • Molecular Targeted Therapy*
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Triple Negative Breast Neoplasms / metabolism*
  • Triple Negative Breast Neoplasms / therapy*
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • Ferric Compounds
  • Intercellular Adhesion Molecule-1
  • ferric oxide