Endothelial cells in tumor vessels express angiogenic markers that are not present in normal vessels. We have developed an in vivo selection system in which phage capable of homing into tumors are recovered from a phage display peptide library following intravenous administration. Using this strategy, we have recently isolated tumor-homing phage displaying the peptide motif asparagine-glycine-arginine (NGR). These NGR-containing peptides bind selectively to angiogenic tumor vessels. A strong candidate receptor for the NGR-containing peptides in tumor vasculature is closely related to CD13/aminopeptidase N (termed NGR receptor). In the work proposed here, we will determine whether the NGR receptor is related or identical to CD13/aminopeptidase. We will investigate its pattern of expression and activity in tumor-induced angiogenesis and determine whether CD13 is also expressed in other forms of angiogenesis. Finally, we will examine the effects of inhibitors of CD13 on tumor growth. These findings will clarify the role of CD13 in angiogenesis and may lead to the development of new anti-tumor therapeutic strategies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA078512-04
Application #
6376850
Study Section
Pathology B Study Section (PTHB)
Project Start
1999-09-01
Project End
2003-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
4
Fiscal Year
2001
Total Cost
$266,456
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Dentistry
Type
Other Domestic Higher Education
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Staquicini, Fernanda I; Tandle, Anita; Libutti, Steven K et al. (2008) A subset of host B lymphocytes controls melanoma metastasis through a melanoma cell adhesion molecule/MUC18-dependent interaction: evidence from mice and humans. Cancer Res 68:8419-28
Sergeeva, Anna; Kolonin, Mikhail G; Molldrem, Jeffrey J et al. (2006) Display technologies: application for the discovery of drug and gene delivery agents. Adv Drug Deliv Rev 58:1622-54
Yao, Virginia J; Ozawa, Michael G; Trepel, Martin et al. (2005) Targeting pancreatic islets with phage display assisted by laser pressure catapult microdissection. Am J Pathol 166:625-36
Marchio, Serena; Lahdenranta, Johanna; Schlingemann, Reinier O et al. (2004) Aminopeptidase A is a functional target in angiogenic blood vessels. Cancer Cell 5:151-62
Chen, Limor; Zurita, Amado J; Ardelt, Peter U et al. (2004) Design and validation of a bifunctional ligand display system for receptor targeting. Chem Biol 11:1081-91
Arap, Marco A; Lahdenranta, Johanna; Mintz, Paul J et al. (2004) Cell surface expression of the stress response chaperone GRP78 enables tumor targeting by circulating ligands. Cancer Cell 6:275-84
Kolonin, Mikhail G; Saha, Pradip K; Chan, Lawrence et al. (2004) Reversal of obesity by targeted ablation of adipose tissue. Nat Med 10:625-32
Bhagwat, S V; Lahdenranta, J; Giordano, R et al. (2001) CD13/APN is activated by angiogenic signals and is essential for capillary tube formation. Blood 97:652-9