Stromal cell-derived factor-1α-induced cell proliferation and its possible regulation by CD26/dipeptidyl peptidase IV in endometrial adenocarcinoma
Stromal cell-derived factor-1α-induced cell proliferation and its possible regulation by CD26/dipeptidyl peptidase IV in endometrial adenocarcinoma
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DOI：
10.1002/ijc.20183
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发表时间：
2004-07-10
影响因子：
6.4
通讯作者：
Mizutani, S
中科院分区：
文献类型：
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作者：
Mizokami, Y;Kajiyama, H;Mizutani, S
CD26/二肽基肽酶IV(DPPIV)是一种广泛表达的110kD膜结合型胞外肽酶，在人类恶性肿瘤的发生发展和T细胞生物学中具有多种功能。最近的研究表明，基质细胞衍生因子-Iα(SDF-Iα)是CD26/DPPIV的良好底物，在多种实体肿瘤中均有表达，并参与肿瘤的发生和转移。我们研究了SDF-Ipha及其相应受体CXCR4在子宫内膜癌(EMCA)组织中的表达及其在CD26/DPPIV调控下对EMCA细胞的作用。我们发现SDF-Ipha和CXCR4在人EMCA中有表达，与CD26/DPPIV相比，CD26/DPPIV在3级EMCA中的免疫反应性显著降低。此外，CD26/DPPIV转基因的EMCA细胞中外源SDF-Ipha的浓度显著低于载体转染组。此外，外源性SDF-Ipha以浓度依赖的方式显著刺激载体转染组细胞的增殖。相反，在CD26/DPPIV转基因细胞中，外源性SDF-Ipha对细胞的增殖没有明显的影响。这是首次报道在实体瘤中SDF-Ipha/CXCR4通路与CD26/DPPIV之间存在直接联系，提示CD26/DPPIV可能直接调节SDF-Ipha诱导的各种功能。(C)2004年Wiley-Liss公司
CD26/dipeptidylpeptidase IV (DPPIV) is a 110 kD membrane-bound extracellular peptidase with ubiquitous expressions, and has a variety of functional properties in the development of human malignancies as well as T-cell biology. According to recent reports, stromal cell derived factor-Ialpha (SDF-Ialpha), which is a good substrate for CD26/DPPIV, is expressed in various solid tumors and is involved in tumor development or metastasis. We investigated the expression of SDF-Ialpha and its corresponding receptor, CXCR4, in human endometrial carcinoma (EMCA) tissues and the function of SDF-Ialpha on EMCA cells with its regulation by CD26/DPPIV. We demonstrated that SDF-Ialpha and CXCR4 were expressed in human EMCA, and these immunoreactivities were significantly low in Grade 3 EMCA, which was similar to that of CD26/DPPIV, compared to those in Grade I and Grade 2. Additionally, exogenous SDF-Ialpha concentration was significantly lower in CD26/DPPIV-transfected EMCA cells than that in vector-transfected cells. Moreover, exogenous SDF-Ialpha significantly stimulated cell proliferation in vector-transfected cells in a concentration dependent manner. In contrast, in CD26/DPPIV-transfected cells, there was no apparent effect on proliferation shown by the addition of exogenous SDF-Ialpha. This is the first report showing a direct link between the SDF-Ialpha/CXCR4 pathway with CD26/DPPIV in solid tumors, suggesting that CD26/DPPIV is likely to directly modulate various SDF-Ialpha induced functions. (C) 2004 Wiley-Liss, Inc.