Suppression of metastasis due to regulation of Aminopeptidase-N

本研究旨在系统探讨细胞表面蛋白可能参与细胞运动和血管生成的调控，并进一步确定与恶性肿瘤有关的细胞表面分子。我们使用抑制细胞运动的功能性单克隆抗体（mab）来解决这些问题。此外，我们选择了抑制人脐静脉内皮细胞迁移和管形成的MAb。我们建立了抑制细胞运动和体外血管生成的小鼠单抗MH8-11。该表位是一个165-kD蛋白，测序分析显示它与氨基肽酶N (APN)/ CD13 （CD13）几乎相同。对114例结肠癌患者的APN/CD13表达进行了评估。APN/CD13阳性67例，阴性47例。APN/CD13表达阳性肿瘤患者的无病生存率和总生存率显著低于APN/CD13表达阴性肿瘤患者（P分别为0.014和0.033）。在47例淋巴结阳性患者中，APN/CD13表达阴性的患者生存率优于APN/CD13表达阳性的患者。我们的数据表明，APN/CD13参与体外细胞运动和血管生成，因此APN/CD13的表达可能是结阳性结肠癌患者预后不良的有用指标。此外，我们还研究了50例胰腺癌中APN/CD13的表达和肿瘤内微血管密度（IMD）的变化。APN/CD13也与IMD的增加显著相关（p= 0.92）。APN/CD13表达患者的中位生存时间明显短于APN/CD13不表达患者（p=0.009），多因素分析显示APN/CD13状态是一个显著的独立因素（p=0.016）。APN/CD13可能是胰腺癌患者新的预后标志物，也是胰腺癌的血管生成因子。少

The aims of this study were to systematically investigate the possible involvement of proteins at the cell surface in controlling cell motility and angiogenesis, and further identify the cell surface molecules involved in malignant tumors. We addressed these issues using functional monoclonal antibodies (MAbs), which inhibit cell motility. In addition, we selected MAb that inhibits human umbilical vein endothelial cell migration and tube formation. We established a murine MAb MH8-11, which inhibits cell motility and in vitro angiogenesis. This epitope was a 165-kD protein and the sequencing analysis revealed that it was almost identical to aminopeptidase N (APN)/cluster of differentiation 13 (CD13). APN/CD13 expression was evaluated in colon cancers from 114 patients. Sixty-seven patients were positive and 47 patients were negative for APN/CD13.The disease-free and overall survival rate for patients with positive APN/CD13 expression tumors was significantly lower than that for patients … More with negative APN/CD13 expression tumors (P 0.014, 0.033 ; respectively). Among the 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. Our data suggest that APN/CD13 is involved in cell motility and angiogenesis in vitro, and the expression of APN/CD13 may thus be a useful indicator of a poor prognosis for node-positive patients with colon cancer. In addition, we investigated the expression of APN/CD13 and the intratumor microvessel density (IMD) in 50 patients with pancreatic carcinoma. APN/CD13 was also significantly associated with an increase of the IMD (p=O.OO2). The median survival time of patients with APN/CD13 expression was significantly shorter than that of patients without APN/ CD13 expression (p=0.009), and multivariate analysis showed that the APN/CD13 status was a significant independent factor (p=0.016). APN/CD13 may be a new prognostic marker for patients with pancreatic carcinoma as well as being an angiogenic factor for this cancer. Less