Abstract
Cancer chemotherapy targeted to angiogenic vessels is expected to cause indirect tumor regression through the damage of the neovasculature without the induction of drug resistance. To develop a tool for neovasculature-specific drug delivery, we isolated novel peptides homing to angiogenic vessels formed by a dorsal air sac method from a phage-displayed peptide library. Three distinct phage clones that markedly accumulated in murine tumor xenografts presented PRPGAPLAGSWPGTS-, DRWRPALPVVLFPLH- or ASSSYPLIHWRPWAR-peptide respectively. After the determination of the epitope sequences of these peptides, we modified liposomes with epitope penta-peptides. Liposome modified with APRPG-peptide showed high accumulation in murine tumor xenografts, and APRPG-modified liposome encapsulating adriamycin effectively suppressed experimental tumor growth. Finally, specific binding of APRPG-modified liposome to human umbilical endothelial cells, and that of PRP-containing peptide to angiogenic vessels in human tumors, i.e., islet cell tumor and glioblastoma, were demonstrated. The present study indicates the usefulness of APRPG-peptide as a tool for anti-neovascular therapy, a novel modality of cancer treatment.
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References
Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM . 1997 Science 275: 964–967
Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM . 1999 EMBO J. 18: 3964–3972
Asai T, Kurohane K, Shuto S, Awano H, Matsuda A, Tsukada H, Namba Y, Okada S, Oku N . 1998 Biol. Pharm. Bull. 21: 766–771
Arap W, Pasqualini R, Ruoslahti E . 1998 Science 279: 377–380
Boehm T, Folkman J, Browder T, O'Reilly MS . 1997 Nature 390: 404–407
Browder T, Butterfield CE, Kraling BM, Shi B, Marshall B, O'Reilly MS, Folkman J . 2000 Cancer Res. 60: 1878–1886
Brower V . 1999 Nat Biotechnol. 17: 963–968
Brown JM, Giaccia AJ . 1998 Cancer Res. 58: 1408–1416
Cao Y, Linden P, Farnebo J, Cao R, Eriksson A, Kumar, V, Qi JH, Claesson-Welsh L, Alitalo K . 1998 Proc. Natl. Acad. Sci. USA 95: 14389–14394
Eliceiri BP, Cheresh DA . 1999 J. Clin. Invest. 103: 1227–1230
Gho YS, Lee JE, Oh KS, Bae DG, Chae CB . 1997 Cancer Res. 57: 3733–3740
Hanahan D . 1997 Science 277: 48–50
Healy JM, Murayama O, Maeda T, Yoshino K, Sekiguchi K, Kikuchi M . 1995 Biochemistry 34: 3948–3955
Huang X, Molema G, King S, Watkins L, Edgington TS, Thorpe PE . 1997 Science 275: 547–550
Ishikawa D, Kikkawa H, Ogino K, Hirabayashi Y, Oku N, Taki T . 1998 FEBS Lett. 441: 20–24
Ito H, Rovira II, Bloom ML, Takeda K, Ferrans VJ, Quyyumi AA, Finkel T . 1999 Cancer Res. 59: 5875–5877
Koivunen E, Gay DA, Ruoslahti E . 1993 J. Biol. Chem. 268: 20205–20210
Kurohane K, Tominaga A, Sato K, North JR, Namba Y, Oku N . 2001 Cancer Lett. 167: 49–56
Langer R . 1998 Nature 392: 5–10
Martens CL, Cwirla SE, Lee RY, Whitehorn E, Chen EY, Bakker A, Martin EL, Wagstrom C, Gopalan P, Smith CW, Tate E, Koller KJ, Schatz PJ, Dower WJ, Barrett RW . 1995 J. Biol. Chem. 270: 21129–21136
Nishi T, Budde RJA, McMurray JS, Obeyeskere NU, Safdar N, Levin VA, Saya H . 1996 FEBS Lett. 399: 237–240
Oku N . 1999a Adv. Drug Deliv. Rev. 40: 63–73
Oku N . 1999b Adv. Drug Deliv. Rev. 37: 53–61
Oku N, Doi K, Namba Y, Okada S . 1994 Int. J. Cancer 58: 415–419
Oku N, Namba Y, Okada S . 1992 Biochim. Biophys. Acta 1126: 255–260
O'Reilly MS, Holmgren L, Chen C, Folkman J . 1996 Nat. Med. 2: 689–692
Pasqualini R, Koivunen E, Ruoslahti E . 1997 Nat. Biotechnol. 15: 542–546
Pasqualini R, Ruoslahti E . 1996 Nature 380: 364–366
Scott JK, Smith GP . 1990 Science 249: 386–390
Skobe M, Rockwell P, Goldstein N, Vosseler S, Fusenig NE . 1997 Nat. Med. 3: 1222–1227
St Croix B, Rago C, Velculescu V, Traverso G, Romans KE, Montgomery E, Lal A, Riggins GJ, Lengauer C, Vogelstein B, Kinzler KW . 2000 Science 289: 1197–1202
Takikawa M, Kikkawa H, Asai T, Yamaguchi N, Ishikawa D, Tanaka M, Ogino K, Taki T, Oku N . 2000 FEBS Lett. 446: 381–384
Viti F, Tarli L, Giovannoni L, Zardi L, Neri D . 1999 Cancer Res. 59: 347–352
Zetter BR . 1997 Nat. Biotechnol. 15: 1243–1244
Acknowledgements
The authors thank Dr Yoji Ikawa at RIKEN for commenting on the manuscript. This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science and by Terumo Life Science Foundation. T Asai is a Research Fellow of the Japan Society for the Promotion of Science.
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Oku, N., Asai, T., Watanabe, K. et al. Anti-neovascular therapy using novel peptides homing to angiogenic vessels. Oncogene 21, 2662–2669 (2002). https://doi.org/10.1038/sj.onc.1205347
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DOI: https://doi.org/10.1038/sj.onc.1205347
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