Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis.
Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis.
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发表时间：
2000-02
期刊：
影响因子：
11.2
通讯作者：
R. Pasqualini;E. Koivunen;R. Kain;J. Lahdenranta;J. Lahdenranta;M. Sakamoto;A. Stryhn;R. Ashmun
中科院分区：
文献类型：
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作者：
R. Pasqualini;E. Koivunen;R. Kain;J. Lahdenranta;J. Lahdenranta;M. Sakamoto;A. Stryhn;R. Ashmun
显示具有NGR序列基序的表面肽的噬菌体在体内选择性地返回肿瘤血管。与游离药物相比，与NGR肽偶联的药物具有更强的抗肿瘤作用[j]。[j].环境科学与技术，2004(2):1 - 7。我们发现肿瘤血管中NGR肽的受体是氨肽酶N （APN，也称为CD13）。NGR噬菌体特异性结合免疫捕获的APN和在其表面表达APN的细胞。抗APN抗体抑制NGR噬菌体在体内的肿瘤归巢。免疫组化染色显示APN在小鼠和人肿瘤内皮细胞中表达上调。在另一种血管生成组织黄体中，血管也表达APN，但在相同条件下染色的其他各种正常组织的血管中未检测到APN。APN拮抗剂特异性抑制绒毛膜尿囊膜和视网膜血管生成，抑制肿瘤生长。因此，APN参与血管生成，可以作为药物进入肿瘤和抑制血管生成的靶标。
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.