A tumor-homing peptide with a targeting specificity related to lymphatic vessels.
Blood vessels of tumors carry specific markers that are usually angiogenesis-related. We previously used phage-displayed peptide libraries in vivo to identify peptides that home to tumors through the circulation and that specifically bind to the endothelia of tumor blood vessels. Here we devised a phage screening procedure that would favor tumor-homing to targets that are accessible to circulating phage, but are not blood vessels. Screening on MDA-MB-435 breast carcinoma xenografts yielded multiple copies of a phage that displays a cyclic 9-amino-acid peptide, LyP-1. Homing and binding to tumor-derived cell suspensions indicated that LyP-1 also recognizes an osteosarcoma xenograft, and spontaneous prostate and breast cancers in transgenic mice, but not two other tumor xenografts. Fluorescein-labeled LyP-1 peptide was detected in tumor structures that were positive for three lymphatic endothelial markers and negative for three blood vessel markers. LyP-1 accumulated in the nuclei of the putative lymphatic cells, and in the nuclei of tumor cells. These results suggest that tumor lymphatics carry specific markers and that it may be possible to specifically target therapies into tumor lymphatics.
Laakkonen
Pirjo
P
Cancer Research Center, The Burnham Institute, La Jolla, California, USA.
Porkka
Kimmo
K
Hoffman
Jason A
JA
Ruoslahti
Erkki
E
D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000473:pathology*; D002467:Cell Nucleus / Q000473:pathology; D005260:Female; D005452:Fluoresceins / Q000493:pharmacokinetics; D006801:Humans; D008208:Lymphatic System / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008822:Mice, Transgenic; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000473:pathology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D005452:Fluoresceins; C461500:LyP-1 protein, mouse; D019151:Peptide Library; D010456:Peptides, Cyclic