Dipeptidyl peptidase IV overexpression induces up-regulation of E-cadherin and tissue inhibitors of matrix metalloproteinases, resulting in decreased invasive potential in ovarian carcinoma cells.
Dipeptidyl peptidase IV overexpression induces up-regulation of E-cadherin and tissue inhibitors of matrix metalloproteinases, resulting in decreased invasive potential in ovarian carcinoma cells.
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发表时间：
2003-05
期刊：
影响因子：
11.2
通讯作者：
H. Kajiyama;F. Kikkawa;E. Khin;K. Shibata;K. Ino;S. Mizutani
中科院分区：
文献类型：
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作者：
H. Kajiyama;F. Kikkawa;E. Khin;K. Shibata;K. Ino;S. Mizutani
二肽基肽酶 IV (DPPIV/CD26) 是一种多功能细胞表面氨肽酶，广泛表达于不同细胞类型中。我们之前的研究证明了 DPPIV 表达与腹腔注射减少之间可能存在联系。卵巢癌的传播和侵袭潜力的丧失。在本报告中，我们更详细地研究了 DPPIV 的抗侵袭能力的机制。 5种独立卵巢癌细胞系中E-cadherin和β-catenin的表达与DPPIV表达呈正相关。将 DPPIV cDNA 引入具有低 DPPIV 表达的卵巢癌细胞系 (SKOV3) 中，增强了 E-钙粘蛋白和 β-连环蛋白的表达，细胞形态从成纤维细胞和运动表型转变为上皮表型。此外，基质金属蛋白酶2和膜1型基质金属蛋白酶（与侵袭和转移潜能相关的重要标志物）显着降低。相反，DPPIV 转染上调了基质金属蛋白酶的组织抑制剂。此外，在 DPPIV 过表达细胞中观察到丝裂原激活蛋白激酶亚型（细胞外信号调节激酶）的磷酸化水平受到抑制。据我们所知，这是第一个证据表明增加 DPPIV 表达可能通过上调 E-钙粘蛋白和基质金属蛋白酶的组织抑制剂来延长生存期。
Dipeptidyl peptidase IV (DPPIV/CD26) is a multifunctional cell surface aminopeptidase that is widely expressed in different cell types. Our previous study demonstrated a possible link between DPPIV expression and decreased i.p. dissemination and loss of invasive potential of ovarian carcinoma. In this report, we examined the mechanisms of the anti-invasive ability of DPPIV in greater detail. Expression of E-cadherin and beta-catenin was positively correlated with DPPIV expression among five independent ovarian carcinoma cell lines. The introduction of DPPIV cDNA into an ovarian carcinoma cell line (SKOV3) with low DPPIV expression enhanced the expression of E-cadherin and beta-catenin, with a cellular morphological change from a fibroblastic and motile phenotype to an epithelial phenotype. In addition, matrix metalloproteinase 2 and membrane type 1 matrix metalloproteinase, important markers associated with invasive and metastatic potential, were remarkably reduced. In contrast, tissue inhibitors of matrix metalloproteinases were up-regulated by DPPIV transfection. Furthermore, suppression of the phosphorylation levels of mitogen-activated protein kinase isoform, extracellular signal-regulated kinase, was observed in DPPIV-overexpressing cells. To our knowledge, this is the first evidence that increasing DPPIV expression may contribute to prolonged survival by up-regulation of E-cadherin and tissue inhibitors of matrix metalloproteinases.