Detection and downregulation of type I IGF receptor expression by antibody-conjugated quantum dots in breast cancer cells

Breast Cancer Res Treat. 2009 Mar;114(2):277-85. doi: 10.1007/s10549-008-0014-5. Epub 2008 Apr 17.

Abstract

The type I insulin-like growth factor (IGF) receptor (IGF1R) is a transmembrane tyrosine kinase involved in breast cancer proliferation, survival, and metastasis. Several monoclonal antibodies directed against the receptor are in clinical trials. In order to develop a methodology to detect and measure IGF1R levels in breast cancer cells, we covalently conjugated an IGF1R antibody, AVE-1642, with quantum dots (Qdots), which are nanocrystals that emit fluorescence upon excitation. AVE-1642 Qdots only bound to cells that express IGF1R, and measured IGF1R levels by fluorescence emission at 655 nm. After binding to the cell surface, AVE-1642 Qdots underwent receptor mediated endocytosis, localized to endosome, and later translocated into the nucleus. Treating MCF-7 cells with AVE-1642 Qdots, but not unconjugated Qdots alone, downregulated IGF1R levels and rendered cells refractory to IGF-I stimulation. Furthermore, cell proliferation was slightly inhibited by AVE-1642 Qdots, but not the unconjugated Qdots. Our data suggest that AVE-1642 Qdots can be used to detect IGF1R expression and measure changes in cell surface receptor levels. In addition, the inhibitory effect of AVE-1642 Qdots to cell proliferation implies that it may serve as a traceable therapeutic agent.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Blotting, Western
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line
  • Cell Membrane / metabolism*
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Flow Cytometry
  • Homozygote
  • Humans
  • Insulin-Like Growth Factor I / pharmacology
  • Mice
  • Mice, Knockout
  • Quantum Dots*
  • Receptor, IGF Type 1 / metabolism*

Substances

  • Antibodies, Monoclonal
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1