Up-regulation of CXC chemokines and their receptors: implications for proinflammatory microenvironments of ovarian carcinomas and endometriosis
Up-regulation of CXC chemokines and their receptors: implications for proinflammatory microenvironments of ovarian carcinomas and endometriosis
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DOI：
10.1016/j.humpath.2007.03.023
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发表时间：
2007-11-01
期刊：
影响因子：
3.3
通讯作者：
Kimura, Sadao
中科院分区：
文献类型：
--
作者：
Furuya, Mitsuko;Suyama, Takahito;Kimura, Sadao
子宫内膜异位症上皮细胞的分子异常及其与卵巢癌发生的相关性已得到充分研究。另一方面，子宫内膜异位症和卵巢癌之间促炎微环境的差异尚未得到充分记录。在本研究中，使用定量逆转录酶聚合酶链反应和免疫组织化学比较了 12 例卵巢癌、8 例子宫内膜异位症和 6 例正常卵巢中 CXC 趋化因子（IL-8、ENA-78、GRO-α、1-TAC、Mig 和 SDF-1）及其受体（CXCR2、CXCR3 和 CXCR4）的表达模式。还研究了体外卵巢癌细胞中 CXCR3 介导的信号传导。在定量逆转录酶聚合酶链反应中，ENA-78 在子宫内膜异位症和癌症中均上调，而 I-TAC 仅在癌症中检测到。 CXCR3 在癌症和子宫内膜异位症中均上调。然而，免疫组织化学研究表明，CXCR3 在癌症中的定位与子宫内膜异位症中的定位明显不同。在癌与子宫内膜异位症共存的病例中，良性病变中的CXCR3阳性淋巴细胞随着CXCR3阳性肿瘤细胞取代组织而成比例减少。 CXCR3也在体外卵巢癌细胞系中检测到。施用干扰素γ（IFN-γ）诱导趋化因子可诱导这些癌细胞中的细胞外信号调节激酶磷酸化。结果表明CXC趋化因子可能以不同的方式促进卵巢癌和子宫内膜异位症的进展。癌细胞中 IFN-γ 诱导性趋化因子和 CXCR3 的异常表达与 CXCR3 阳性免疫细胞减少相关，提出了一种可能性：IFN-γ 诱导性趋化因子可能不会发挥有效的抗肿瘤免疫反应，但它们可能有利于肿瘤进展。 (c) 2007 Elsevier Inc. 保留所有权利。
Molecular abnormalities in the epithelial cells of endometriosis and their relevance to carcinogenesis of the ovary have been well studied. On the other hand, the differences of proinflammatory microenvironments between endometriosis and ovarian carcinomas have not been well documented yet. In this study, the expression patterns of CXC chemokines (IL-8, ENA-78, GRO-alpha, 1-TAC, Mig, and SDF-1) and their receptors (CXCR2, CXCR3, and CXCR4) were compared among 12 ovarian carcinomas, 8 endometriosis, and 6 normal ovaries using quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. The CXCR3-mediated signaling in ovarian carcinoma cells in vitro was also investigated. In quantitative reverse transcriptase polymerase chain reaction, ENA-78 was up-regulated both in endometriosis and carcinomas, whereas I-TAC was detected exclusively in carcinomas. CXCR3 was up-regulated both in carcinomas and endometriosis. However, immunohistochemical studies revealed that the localization of CXCR3 in carcinomas was distinctively different from that in endometriosis. In carcinoma-endometriosis coexisting cases, CXCR3-positive lymphocytes in benign lesions decreased in proportion as CXCR3-positive tumor cells replaced the tissues. CXCR3 was also detected in ovarian carcinoma cell lines in vitro. Administration of interferon gamma (IFN-gamma)-inducible chemokines induced extracellular signal-regulated kinase phosphorylation in these carcinoma cells. The results indicated that CXC chemokines might contribute to the progression of ovarian carcinomas and endometriosis in different manners. Aberrant expression of IFN-gamma-inducible chemokines and CXCR3 in carcinoma cells in association with reduced CXCR3-positive immune cells raised the possibility that IFN-gamma-inducible chemokines might not exert effective antitumor immune responses but that they might work in favor of tumor progression. (c) 2007 Elsevier Inc. All rights reserved.