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(Chest. 2005;128:596S-600S.)
© 2005 American College of Chest Physicians

Phenotypic Diversity of the Lung Vasculature in Experimental Models of Metastases*

Yun Oh; Imran Mohiuddin; Yan Sun; Joseph B. Putnam, Jr; Waun Ki Hong; Wadih Arap, MD, PhD and Renata Pasqualini, PhD

* From the Departments of Thoracic/Head & Neck Medical Oncology (Drs. Oh and Hong), Thoracic Surgery (Drs. Mohiuddin and Putnam), and Genitourinary Medical Oncology (Drs. Sun, Arap, and Pasqualini), The University of Texas M.D. Anderson Cancer Center, Houston, TX.

Correspondence to: Wadih Arap, MD, PhD, or Renata Pasqualini, PhD, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: warap{at}mdanderson.org or rpasqual{at}mdanderson.org

In vivo phage display is a screening method in which peptides homing to specific vascular beds are selected after IV administration of a random peptide library. This strategy has revealed a vascular address system that allows tissue-specific targeting of normal blood vessels and angiogenesis-related targeting of tumor blood vessels by selected peptides. Many vascular receptors or "addresses" targeted by homing peptides have been identified. One such vascular receptor of normal lung endothelium is membrane dipeptidase (MDP), which was found by in vivo phage display to bind the tripeptide motif gly-phe-glu (GFE). Our studies with GFE peptide and lung vasculature suggest that MDP mediates cancer cell adhesion to lung vasculature and the development of lung metastases, but that MDP is not present in the vasculature of lung metastases. MDP appears to occupy a vascular distribution that is similar to the pulmonary artery circulation. These results demonstrate the promise of defining critical functional and anatomic characteristics of endothelial cells in lung and other organs by in vivo phage display.

Key Words: lung endothelium • membrane dipeptidase • metastasis • phage display • random peptide library • vascular targeting






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