Targeting bladder tumor cells in vivo and in the urine with a peptide identified by phage display.
Bladder cancer is one of the most common tumors of the genitourinary tract. Here, we use phage display to identify a peptide that targets bladder tumor cells. A phage library containing random peptides was screened for binding to cells from human bladder tumor xenografts. Phage clones were further selected for binding to a bladder tumor cell line in culture. Six clones displaying the consensus sequence CXNXDXR(X)/(R)C showed selective binding to cells from primary human bladder cancer tissue. Of these, the CSNRDARRC sequence was selected for further study as a synthetic peptide. Fluorescein-conjugated CSNRDARRC peptide selectively bound to frozen sections of human bladder tumor tissue, whereas only negligible binding to normal bladder tissue was observed. When the fluorescent peptide was introduced into the bladder lumen, in a carcinogen-induced rat tumor model, it selectively bound to tumor epithelium. Moreover, when the peptide was intravenously injected into the tail vein, it homed to the bladder tumor but was not detectable in normal bladder and control organs. Next, we examined whether the peptide can detect tumor cells in urine. The fluorescent peptide bound to cultured bladder tumor cells but not to other types of tumor cell lines. Moreover, it bound to urinary cells of patients with bladder cancer, while showing little binding to urinary cells of patients with inflammation or healthy individuals. The CSNRDARRC peptide may be useful as a targeting moiety for selective delivery of therapeutics and as a diagnostic probe for the detection of bladder cancer.
Lee
Seung-Min
SM
Department of Biochemistry, School of Medicine, Kyungpook National University, 101 Dongin-Dong, Jung-Gu, Daegu 700-421, Korea.
Lee
Eun-Ju
EJ
Hong
Hai-Yan
HY
Kwon
Mi-Kyung
MK
Kwon
Tae-Hwan
TH
Choi
Je-Yong
JY
Park
Rang-Woon
RW
Kwon
Tae-Gyun
TG
Yoo
Eun-Sang
ES
Yoon
Gil-Suk
GS
Kim
In-San
IS
Ruoslahti
Erkki
E
Lee
Byung-Heon
BH
D000818:Animals; D001435:Bacteriophages / Q000378:metabolism; D001667:Binding, Competitive; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000652:urine; D002478:Cells, Cultured; D016384:Consensus Sequence; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D007158:Immunologic Techniques; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism*; D009842:Oligopeptides / Q000302:isolation & purification / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D019151:Peptide Library; D011485:Protein Binding; D051381:Rats; D013379:Substrate Specificity; D001743:Urinary Bladder / Q000166:cytology / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000652:urine
D009363:Neoplasm Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D019151:Peptide Library