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

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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.

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Acknowledgments

We thank Dr. Renato Baserga for R- cells. We are grateful to the services from the University of Minnesota Cancer Center Flow Cytometry Shared Resource and Confocal Microscopy Facility.Grant support: Department of Defense Post-doctoral Grant BC050548 (HZ) and R01CA74285 (DY), and Cancer Center Support Grant P30 077598.

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Authors and Affiliations

  1. University of Minnesota Cancer Center, University of Minnesota, MMC 806, 420 Delaware St SE, Minneapolis, MN, 55455, USA

    Hua Zhang, Deepali Sachdev & Douglas Yee

  2. Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, 55455, USA

    Chun Wang

  3. Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN, 55455, USA

    Allison Hubel

  4. Sanofi-Aventis, Paris, France

    Martine Gaillard-Kelly

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  1. Hua Zhang
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  2. Deepali Sachdev
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  3. Chun Wang
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  4. Allison Hubel
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  6. Douglas Yee
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Correspondence to Douglas Yee.

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Zhang, H., Sachdev, D., Wang, C. et al. Detection and downregulation of type I IGF receptor expression by antibody-conjugated quantum dots in breast cancer cells. Breast Cancer Res Treat 114, 277–285 (2009). https://doi.org/10.1007/s10549-008-0014-5

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  • DOI: https://doi.org/10.1007/s10549-008-0014-5

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