Suppression of metastasis due to regulation of Aminopeptidase-N

通过氨肽酶-N 的调节抑制转移

• 批准号: 12470279
• 负责人: ISHIDA Hisao
• 金额: $ 9.41万
• 依托单位: Tazuke Kofukai Medical Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470279/
• 关键词: Aminopeptidase-N; CD13; metastasis; angiogenesis; HUVEC; Aminopeptidase-N(APN); 転移; 血管新生; モノクローナル抗体

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

本研究的目的是系统地研究细胞表面蛋白质可能参与控制细胞运动和血管生成，并进一步鉴定参与恶性肿瘤的细胞表面分子。我们使用抑制细胞运动的功能性单克隆抗体 (MAb) 解决了这些问题。此外，我们选择了抑制人脐静脉内皮细胞迁移和管形成的单克隆抗体。我们建立了一种小鼠单克隆抗体 MH8-11，它能抑制细胞运动和体外血管生成。该表位是一个 165 kD 的蛋白质，测序分析显示它与氨肽酶 N (APN)/分化簇 13 (CD13) 几乎相同。对 114 名患者的结肠癌中的 APN/CD13 表达进行了评估。 67 名患者 APN/CD13 呈阳性，47 名患者呈阴性。APN/CD13 表达阳性肿瘤患者的无病生存率和总生存率显着低于 APN/CD13 表达阴性肿瘤患者（P 分别为 0.014、0.033）。 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 的表达可能是淋巴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 例胰腺癌患者中 APN/CD13 的表达和瘤内微血管密度（IMD）。 APN/CD13 也与 IMD 的增加显着相关 (p=0.002)。 APN/CD13表达的患者中位生存时间显着短于APN/CD13不表达的患者（p=0.009），多变量分析显示APN/CD13状态是显着的独立因素（p=0.016）。 APN/CD13 可能是胰腺癌患者的新预后标志物，也是这种癌症的血管生成因子。较少的

项目成果

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Yagita, M. 等人：“一种新型自然杀伤细胞系 (KHYG-1)，来自携带 p53 点突变的侵袭性自然杀伤细胞白血病患者”白血病。

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Hirasawa, Y., et al.: "Natural autoantibody to MUC1 is a prognostic indicator for non-small cell lung cancer"American Journal of Respiratory and Critical Care Medicine. 161. 589-594 (2000)

Hirasawa, Y. 等人：“MUC1 天然自身抗体是非小细胞肺癌的预后指标”美国呼吸与重症监护医学杂志。