title: A combinatorial approach to the selective capture of circulating malignant epithelial cells by peptide ligands.
abstract: Early detection is critical in the administration of definitive and curative therapy of cancer. However, current detection methods are ineffective at identifying the presence of circulating metastatic cancer cells in the blood because they typically sample only a relatively small volume of blood. One strategy for sampling larger blood volumes would be to capture circulating cells in vivo over an extended period of time. The development of such a method would be substantially facilitated by the identification of peptide ligands that bind selectively to metastatic cancer cells in the blood with high affinity. To identify such ligands a combinatorial peptide library was synthesized on polyethylene acrylamide (PEGA) resin and screened for binding to malignant epithelial cells. Using Biacore, cell binding assays were performed to demonstrate that peptides selected from PEGA bead screen can bind selectively to malignant epithelial cancer cells and not to circulating leukocytes under physiologic shear stress conditions. One peptide, with the sequence QMARIPKRLARH, was used to demonstrate selective labeling of malignant epithelial cells spiked in whole blood. When immobilized on appropriate surfaces, these peptides could be used in both in vivo and ex vivo cell separation devices to efficiently and selectively capture metastatic epithelial cancer cells from flowing blood.
authors.affiliation: The Johns Hopkins University School of Medicine, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Aggarwal
authors.forename: Samuel
authors.initials: S
authors.lastname: Janssen
authors.forename: Randy M
authors.initials: RM
authors.lastname: Wadkins
authors.forename: James L
authors.initials: JL
authors.lastname: Harden
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Denmeade
mesh_terms: D000178:Acrylamides / Q000737:chemistry; D000595:Amino Acid Sequence; D015374:Biosensing Techniques / Q000379:methods*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D008024:Ligands; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000628:therapy; D009360:Neoplastic Cells, Circulating; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011485:Protein Binding; D012235:Rhodamines / Q000494:pharmacology; D013314:Stress, Mechanical; D020349:Surface Plasmon Resonance; D013997:Time Factors; D000099166:Polyacrylamides
chemical_list: D000178:Acrylamides; D008024:Ligands; D019151:Peptide Library; D010455:Peptides; D011092:Polyethylene Glycols; D012235:Rhodamines; C113798:polyethyleneglycol-polyacrylamide copolymer; D000099166:Polyacrylamides