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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)722-727
Number of pages6
JournalCancer Research
Volume60
Issue number3
Publication statusPublished - 2000 Feb 1
Externally publishedYes

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CD13 Antigens
NGR peptide
Peptides
Bacteriophages
Neoplasms
Blood Vessels
Pharmaceutical Preparations
Chorioallantoic Membrane
Corpus Luteum
Retina
Endothelial Cells
Staining and Labeling
Antibodies
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pasqualini, R., Koivunen, E., Kain, R., Lahdenranta, J., Sakamoto, M., Stryhn, A., ... Ruoslahti, E. (2000). Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Cancer Research, 60(3), 722-727.

Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. / Pasqualini, Renata; Koivunen, Erkki; Kain, Renate; Lahdenranta, Johanna; Sakamoto, Michiie; Stryhn, Anette; Ashmun, Richard A.; Shapiro, Linda H.; Arap, Wadih; Ruoslahti, Erkki.

In: Cancer Research, Vol. 60, No. 3, 01.02.2000, p. 722-727.

Research output: Contribution to journalArticle

Pasqualini, R, Koivunen, E, Kain, R, Lahdenranta, J, Sakamoto, M, Stryhn, A, Ashmun, RA, Shapiro, LH, Arap, W & Ruoslahti, E 2000, 'Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis', Cancer Research, vol. 60, no. 3, pp. 722-727.
Pasqualini R, Koivunen E, Kain R, Lahdenranta J, Sakamoto M, Stryhn A et al. Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Cancer Research. 2000 Feb 1;60(3):722-727.
Pasqualini, Renata ; Koivunen, Erkki ; Kain, Renate ; Lahdenranta, Johanna ; Sakamoto, Michiie ; Stryhn, Anette ; Ashmun, Richard A. ; Shapiro, Linda H. ; Arap, Wadih ; Ruoslahti, Erkki. / Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. In: Cancer Research. 2000 ; Vol. 60, No. 3. pp. 722-727.
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