Inhibition of APN/CD13 leads to suppressed progressive potential in ovarian carcinoma cells.
Inhibition of APN/CD13 leads to suppressed progressive potential in ovarian carcinoma cells.
复制标题
DOI：
10.1186/1471-2407-7-140
复制
发表时间：
2007-07-27
期刊：
影响因子：
3.8
通讯作者：
Kikkawa F
中科院分区：
文献类型：
--
作者：
Terauchi M;Kajiyama H;Shibata K;Ino K;Nawa A;Mizutani S;Kikkawa F
氨肽酶 N (APN/CD13) 是一种 150 kDa 金属蛋白酶，是一种普遍表达的多功能细胞表面氨肽酶。最近的研究表明 APN/CD13 在几种人类恶性肿瘤的肿瘤进展中发挥着重要作用。在当前的研究中，我们研究了 APN/CD13 在卵巢癌 (OVCA) 进展中的作用。我们首先在多种 OVCA 细胞系和组织中检测了 APN/CD13 在蛋白质水平上的表达。我们随后研究了 APN/CD13 表达与各种 OVCA 细胞系的侵袭潜力之间是否存在相关性。此外，我们使用 APN/CD13 抑制剂 bestatin 或 APN/CD13 siRNA 转染研究了 APN/CD13 在 OVCA 细胞中的功能。我们证实APN/CD13在OVCA组织和细胞系中存在不同程度的表达。各种OVCA细胞系中APN/CD13表达与迁移潜能呈正相关，相应地增强内源性MMP-2的分泌。随后，我们发现添加bestatin或通过siRNA抑制APN/CD13表达后OVCA细胞的增殖和迁移能力显着下降。此外，在动物模型中，接种 OVCA 细胞后每日腹腔注射贝他汀可减少腹膜传播并延长裸鼠的存活时间。目前的数据表明APN/CD13可能参与OVCA的发生，并提示临床使用贝他汀可能有助于改善卵巢癌患者的预后。
Aminopeptidase N (APN/CD13), a 150-kDa metalloprotease, is a multifunctional cell surface aminopeptidase with ubiquitous expression. Recent studies have suggested that APN/CD13 plays an important role in tumor progression of several human malignancies. In the current study, we investigated the role of APN/CD13 in ovarian carcinoma (OVCA) progression. We first examined the expression of APN/CD13 at the protein level in a variety of OVCA cell lines and tissues. We subsequently investigated whether there was a correlation between APN/CD13 expression and invasive potential of various OVCA cell lines. Moreover, we investigated the function of APN/CD13 in OVCA cells using bestatin, an APN/CD13 inhibitor, or transfection of siRNA for APN/CD13. We confirmed that APN/CD13 was expressed in OVCA tissues and cell lines to various extents. There was a positive correlation between APN/CD13 expression and migratory potential in various OVCA cell lines with accordingly enhanced secretion of endogenous MMP-2. Subsequently, we found a significant decrease in the proliferative and migratory abilities of OVCA cells after the addition of bestatin or the inhibition of APN/CD13 expression by siRNA. Furthermore, in an animal model, daily intraperitoneal administration of bestatin after inoculation of OVCA cells resulted in a decrease of peritoneal dissemination and in prolonged survival of nude mice. The current data indicate the possible involvement of APN/CD13 in the development of OVCA, and suggest that clinical use of bestatin may contribute to better prognosis for ovarian carcinoma patients.
登录
查看更多内容
DOI：
10.1111/j.1525-1438.2006.00657.x
发表时间：
2006-09-01
影响因子：
4.8
作者：
Surowiak, P.;Drags, M.;Lage, H.
通讯作者：
Lage, H.
影响因子：
2.5
作者：
Stange, T;Kettmann, U;Holzhausen, HJ
通讯作者：
Holzhausen, HJ
影响因子：
20.3
作者：
Bhagwat, SV;Petrovic, N;Shapiro, LH
通讯作者：
Shapiro, LH
影响因子：
2.2
作者：
Nishikawa, M;Itakura, A;Kikkawa, F
通讯作者：
Kikkawa, F
影响因子：
4
作者：
Kido, A;Krueger, S;Roessner, A
通讯作者：
Roessner, A