Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis

Renata Pasqualini, Erkki Koivunen, Renate Kain, Johanna Lahdenranta, Michiie Sakamoto, Anette Stryhn, Richard A. Ashmun, Linda H. Shapiro, Wadih Arap, Erkki Ruoslahti

研究成果: Article査読

812 被引用数 (Scopus)

抄録

Phage that display a surface peptide with the NGR sequence motif home selectively to tumor vasculature in vivo. A drug coupled to an NGR peptide has more potent antitumor effects than the free drug [W. Arap et al., Science (Washington DC), 279: 377-380, 1998]. We show here that the receptor for the NGR peptides in tumor vasculature is aminopeptidase N (APN; also called CD13). NGR phage specifically bound to immunocaptured APN and to cells engineered to express APN on their surface. Antibodies against APN inhibited in vivo tumor homing by the NGR phage. Immunohistochemical staining showed that APN expression is up-regulated in endothelial cells within mouse and human tumors. In another tissue that undergoes angiogenesis, corpus luteum, blood vessels also expressed APN, but APN was not detected in blood vessels of various other normal tissues stained under the same conditions. APN antagonists specifically inhibited angiogenesis in chorioallantoic membranes and in the retina and suppressed tumor growth. Thus, APN is involved in angiogenesis and can serve as a target for delivering drugs into tumors and for inhibiting angiogenesis.

本文言語English
ページ(範囲)722-727
ページ数6
ジャーナルCancer Research
60
3
出版ステータスPublished - 2000 2月 1
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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