Subtractive proteomic mapping of the endothelial surface in lung and solid tumours for tissue-specific therapy

Phil Oh, Yan Li, Jingyi Yu, Eberhard Durr, Karolina M. Krasinska, Lucy A. Carver, Jacqueline E. Testa and Jan E. Schnitzer ()
Additional contact information
Phil Oh: Sidney Kimmel Cancer Center
Yan Li: Sidney Kimmel Cancer Center
Jingyi Yu: Sidney Kimmel Cancer Center
Eberhard Durr: Sidney Kimmel Cancer Center
Karolina M. Krasinska: Sidney Kimmel Cancer Center
Lucy A. Carver: Sidney Kimmel Cancer Center
Jacqueline E. Testa: Sidney Kimmel Cancer Center
Jan E. Schnitzer: Sidney Kimmel Cancer Center

Nature, 2004, vol. 429, issue 6992, 629-635

Abstract: Abstract The molecular complexity of tissues and the inaccessibility of most cells within a tissue limit the discovery of key targets for tissue-specific delivery of therapeutic and imaging agents in vivo. Here, we describe a hypothesis-driven, systems biology approach to identifying a small subset of proteins induced at the tissue–blood interface that are inherently accessible to antibodies injected intravenously. We use subcellular fractionation, subtractive proteomics and bioinformatics to identify endothelial cell surface proteins exhibiting restricted tissue distribution and apparent tissue modulation. Expression profiling and γ-scintigraphic imaging with antibodies establishes two of these proteins, aminopeptidase-P and annexin A1, as selective in vivo targets for antibodies in lungs and solid tumours, respectively. Radio-immunotherapy to annexin A1 destroys tumours and increases animal survival. This analytical strategy can map tissue- and disease-specific expression of endothelial cell surface proteins to uncover novel accessible targets useful for imaging and therapy.

Date: 2004
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DOI: 10.1038/nature02580

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