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.
|Original language||English (US)|
|Number of pages||9|
|Journal||Breast Cancer Research and Treatment|
|State||Published - Mar 2009|
Bibliographical noteFunding Information:
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.
- Breast cancer
- Quantitative measurement
- Quantum dots
- Type I IGF receptor