Dipeptidyl peptidase IV in tumor progression
Dipeptidyl peptidase IV in tumor progression
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DOI：
10.1016/j.bbapap.2004.09.028
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发表时间：
2005-08-01
影响因子：
3.2
通讯作者：
Mizutani, S
中科院分区：
文献类型：
--
作者：
Kikkawa, F;Kajiyama, H;Mizutani, S
二肽基肽酶IV （Dipeptidyl peptidase IV， DPPIV）是一种普遍表达的110 kda糖蛋白。最近的几项研究表明，DPPIV影响几种人类恶性肿瘤的肿瘤进展。我们发现DPPIV高表达的卵巢癌细胞系具有较小的侵袭潜力。此外，将DPPIV cDNA引入来自DPPIV表达很少的浆液性囊腺癌的SKOV3细胞（SKDPIV），可显著降低其迁移和侵袭潜力。此外，接种SKDPIV细胞的裸鼠比接种亲代或载体转染细胞的裸鼠的腹膜传播明显减少，存活时间更长。我们进一步研究了DPPIV抗侵入能力的机制。在5个独立的卵巢癌细胞系中，E-cadherin的表达与DPPIV的表达呈正相关。与亲代细胞和模拟细胞相比，SKDPIV细胞显示E-cadherin的表达增强，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 （MMP-2）和膜I型基质金属蛋白酶（MT1-MMP）在SKDPIV细胞中显著降低，这是与侵袭和转移潜力相关的重要标志物。相比之下，DPPIV转染后，基质金属蛋白酶（TIMPs）的组织抑制因子增强。这些发现提示DPPIV可能通过调节与癌细胞侵袭和进展相关的几个分子的表达水平，在功能上抑制卵巢癌的腹膜传播和进展。(c) 2004 Elsevier B.V.版权所有
Dipeptidyl peptidase IV (DPPIV) is a 110-kDa glycoprotein with ubiquitous expression. Several recent studies have shown that DPPIV affects tumor progression in several human malignancies. We found that ovarian carcinoma cell lines with higher DPPIV expression showed less invasive potential. Furthermore, introduction of DPPIV cDNA into SKOV3 cells (SKDPIV), derived from serous cystadenocarcinoma showing little DPPIV expression, caused a significant decrease in both migration and invasive potential. In addition, nude mice inoculated with SKDPIV cells showed significantly less peritoneal dissemination and longer survival time than those inoculated with parental or vector transfected cells. We further examined the mechanisms of anti-invasive ability of DPPIV. The expression of E-cadherin was positively correlated with DPPIV expression among five independent ovarian carcinoma cell lines. The SKDPIV cells showed enhanced expression of E-cadherin with a cellular morphological change from a fibroblastic and motile phenotype to an epithelial phenotype compared to parental and MOCK cells. In addition, matrix metalloprotemase 2 (MMP-2) and membrane type I matrix metalloprotease (MT1-MMP), which are important markers associated with invasive and metastatic potential, were remarkably reduced in SKDPIV cells. In contrast, tissue inhibitors of matrix metalloprotemases (TIMPs) were enhanced by DPPIV transfection. These findings imply that DPPIV may functionally suppress peritoneal dissemination and progression of ovarian carcinoma by regulating the expression levels of several molecules associated with carcinoma cell invasion and progression. (c) 2004 Elsevier B.V. All rights reserved.