title: Detection and downregulation of type I IGF receptor expression by antibody-conjugated quantum dots in breast cancer cells.
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.
authors.affiliation: University of Minnesota Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Deepali
authors.initials: D
authors.lastname: Sachdev
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.forename: Allison
authors.initials: A
authors.lastname: Hubel
authors.forename: Martine
authors.initials: M
authors.lastname: Gaillard-Kelly
authors.forename: Douglas
authors.initials: D
authors.lastname: Yee
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D006720:Homozygote; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D045663:Quantum Dots; D017526:Receptor, IGF Type 1 / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1