Aminopeptidase N is involved in cell motility and angiogenesis: Its clinical significance in human colon cancer
Aminopeptidase N is involved in cell motility and angiogenesis: Its clinical significance in human colon cancer
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DOI：
10.1053/gast.2002.31095
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发表时间：
2002-02-01
期刊：
影响因子：
29.4
通讯作者：
Miyake, M
中科院分区：
文献类型：
--
作者：
Hashida, H;Takabayashi, A;Miyake, M
背景与目的：细胞运动的分子基础高度复杂，受多个分子系统调控，而血管生成是肿瘤进展的重要生物学成分。本研究的目的是探讨细胞表面蛋白在控制细胞运动和血管生成中的可能作用，并确定与胃肠道肿瘤相关的细胞表面分子。方法：我们使用功能性单抗来解决这些问题，这些单抗可以抑制细胞运动、内皮细胞迁移和管状细胞的形成。此外，我们还研究了该抗原与结肠癌的关系，并显示了该抗原在人类结肠癌中的预后意义。结果：获得了一株能抑制细胞运动和体外血管生成的鼠源性单抗MH8-11。序列分析表明，该表位与氨基肽酶N(APN)/分化簇(CD)13序列基本一致。APN/CD13的表达与肿瘤状态有关(P=0.025)。APN/CD13表达阳性患者的无瘤生存率和总生存率显著低于APN/CD13表达阴性患者(P分别为0.014和0.033)。在47例淋巴结阳性患者中，APN/CD13表达阴性患者的生存率高于APN/CD13表达阳性患者。结论：APN/CD13参与了细胞运动和血管生成，APN/CD13的表达可能是结肠癌患者预后不良的有用指标。
Background & Aims: The molecular basis of cell motility is highly complex and is controlled by a number of molecular systems, whereas angiogenesis is an important biological component of tumor progression. The alms of this study were to investigate the possible involvement of proteins at the cell surface in controlling cell motility and angiogenesis, and to identify the cell surface molecules involved in gastrointestinal tumors. Methods: We addressed these issues using functional monoclonal antibodies, which inhibit cell motility, endothelial cell migration, and tube formation. Furthermore, we investigated the relationship between this antigen and colon cancer, and showed the prognostic significance in human colon cancer. Results: We established a murine monoclonal antibody MH8-11, which inhibits cell motility and in vitro angiogenesis. This epitope was a 165-kilodalton protein, and the sequencing analysis revealed that it was almost identical to aminopeptidase N (APN)/cluster of differentiation (CD) 13. APN/CD13 expression was associated with tumor status (P = 0.025). The disease-free and overall survival rate for patients with positive APN/CD13 expression tumors was significantly lower than that for patients with negative APN/CD13 expression tumors (P = 0.014, 0.033, respectively). Among 47 node-positive patients, the survival rate of patients with negative APN/CD13 expression was better than that of those with positive APN/CD13 expression. Conclusions: Our data suggest that APN/CD13 is involved in cell motility and angiogenesis, and APN/CD13 expression may be a useful indicator of a poor prognosis for node-positive patients with colon cancer.