Antitumor Activity of a Homing Peptide That Targets Tumor Lymphatics and Tumor Cells

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 m...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-06, Vol.101 (25), p.9381-9386
Main Authors: Laakkonen, Pirjo, Åkerman, Maria E., Biliran, Hector, Yang, Meng, Ferrer, Fernando, Karpanen, Terhi, Hoffman, Robert M., Ruoslahti, Erkki
Format: Article
Language:English
Subjects:
Angiogenesis Inhibitors - therapeutic use
Animals
Antibodies
Biological Sciences
Blood vessels
Breast cancer
Breast Neoplasms - blood supply
Breast Neoplasms - pathology
Cell Death - drug effects
Cell Division - drug effects
Cell Hypoxia - drug effects
Cell Line, Tumor
Cell lines
Cultured cells
Endothelial cells
Female
Fluorescence
Humans
Hypoxia
Lymphatic vessels
Lymphatic Vessels - drug effects
Lymphatic Vessels - pathology
Medical research
Melanoma - blood supply
Melanoma - pathology
Mice
Mice, Nude
Peptides
Peptides, Cyclic - therapeutic use
Transplantation, Heterologous
Tumor cell line
Tumors
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Description
Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0403317101