Breast Cancer Research and Treatment

, Volume 114, Issue 2, pp 277–285

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

  • Hua Zhang
  • Deepali Sachdev
  • Chun Wang
  • Allison Hubel
  • Martine Gaillard-Kelly
  • Douglas Yee
Preclinical Study

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.

Key words

Type I IGF receptor Breast cancer Quantum dots Antibody Quantitative measurement 

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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Hua Zhang
    • 1
  • Deepali Sachdev
    • 1
  • Chun Wang
    • 2
  • Allison Hubel
    • 3
  • Martine Gaillard-Kelly
    • 4
  • Douglas Yee
    • 1
  1. 1.University of Minnesota Cancer CenterUniversity of MinnesotaMinneapolisUSA
  2. 2.Department of Biomedical EngineeringUniversity of MinnesotaMinneapolisUSA
  3. 3.Department of Mechanical EngineeringUniversity of MinnesotaMinneapolisUSA
  4. 4.Sanofi-AventisParisFrance

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