title: Antitumor activity of a homing peptide that targets tumor lymphatics and tumor cells.
abstract: LyP-1 is a peptide selected from a phage-displayed peptide library that specifically binds to tumor and endothelial cells of tumor lymphatics in certain tumors. Fluorescein-conjugated LyP-1 and a related peptide, LyP-1b, strongly accumulated in primary MDA-MB-435 breast cancer xenografts and their metastases from i.v. peptide injections, allowing visualization of orthotopic tumors in intact mice. The LyP peptide accumulation coincided with hypoxic areas in tumors. LyP-1 induced cell death in cultured human breast carcinoma cells that bind and internalize the peptide. Melanoma cells that do not bind LyP-1 were unaffected. Systemic LyP-1 peptide treatment of mice with xenografted tumors induced with the breast cancer cells inhibited tumor growth. The treated tumors contained foci of apoptotic cells and were essentially devoid of lymphatics. These results reveal an unexpected antitumor effect by the LyP-1 peptide that seems to be dependent on a proapoptotic/cytotoxic activity of the peptide. As LyP-1 affects the poorly vascularized tumor compartment, it may complement treatments directed at tumor blood vessels.
authors.affiliation: The Burnham Institute, La Jolla, CA 92037.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Laakkonen
authors.forename: Maria E
authors.initials: ME
authors.lastname: Akerman
authors.forename: Hector
authors.initials: H
authors.lastname: Biliran
authors.forename: Meng
authors.initials: M
authors.lastname: Yang
authors.forename: Fernando
authors.initials: F
authors.lastname: Ferrer
authors.forename: Terhi
authors.initials: T
authors.lastname: Karpanen
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.forename: Erkki
authors.initials: E
authors.lastname: Ruoslahti
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D042601:Lymphatic Vessels / Q000187:drug effects / Q000473:pathology*; D008545:Melanoma / Q000098:blood supply / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
chemical_list: D020533:Angiogenesis Inhibitors; C461500:LyP-1 protein, mouse; D010456:Peptides, Cyclic