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巢蛋白表达在血管生成和乳腺癌进展中的作用。

Role of nestin expression in angiogenesis and breast cancer progression.

机构信息

Department of Histology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland.

Breast Unit, Department of Surgical Oncology, Lower Silesian Oncology Centre, 51-612 Wroclaw, Poland.

出版信息

Int J Oncol. 2018 Feb;52(2):527-535. doi: 10.3892/ijo.2017.4223. Epub 2017 Dec 11.

DOI:10.3892/ijo.2017.4223
PMID:29345290
Abstract

Nestin is an intermediate filament protein and a stem cell marker expressed in several tumours. There is growing evidence of an association between the expression level of nestin and the pathogenesis of triple-negative breast cancer (TNBC). Nestin is also expressed in newly forming tumour vessels and is a valuable marker of ongoing angiogenesis. In this study, we aimed to evaluate the prognostic value of nestin expression in breast tumour cells and to determine whether this expression influences angiogenesis. Immunohistochemical (IHC) analyses were carried out on 124 cases of invasive ductal carcinoma (IDC) of the breast with a panel of murine monoclonal antibodies against nestin, CD31, CD34, SOX-18 and Ki‑67. We evaluated nestin expression in tumour and endothelial cells, Ki‑67 in tumour cells, and CD31, CD34 and SOX-18 in endothelial cells. Our results demonstrated that nestin expression in tumour cells correlated with the area and number of vessels expressing nestin, CD31, CD34 and SOX-18. We also found a positive correlation between nestin-expressing vessels and SOX-18-expressing vessels. Our results are consistent with those of previous studies, in which nestin expression in endothelial cells was shown to be strongly associated with triple-negative subtype, poorly differentiated G3 tumours, a higher proliferation index and a shorter overall survival. Nestin expression was also examined in human breast cancer cell lines (MCF-7, SK-BR-3, MDA‑MB‑231 and BO2 cells) representing a different level of tumour aggressiveness and reflecting histological grade. A higher nestin protein level was observed in more aggressive MDA‑MB‑231 and BO2 cells than in MCF-7 and SK-BR-3 cells.

摘要

巢蛋白是一种中间丝蛋白和干细胞标志物,在几种肿瘤中表达。越来越多的证据表明巢蛋白的表达水平与三阴性乳腺癌(TNBC)的发病机制有关。巢蛋白也在新形成的肿瘤血管中表达,是血管生成的有价值标志物。在这项研究中,我们旨在评估巢蛋白在乳腺肿瘤细胞中的表达对预后的影响,并确定这种表达是否影响血管生成。我们使用一组针对巢蛋白、CD31、CD34、SOX-18 和 Ki-67 的鼠单克隆抗体,对 124 例浸润性导管癌(IDC)进行了免疫组织化学(IHC)分析。我们评估了肿瘤细胞和内皮细胞中的巢蛋白表达、肿瘤细胞中的 Ki-67 表达以及内皮细胞中的 CD31、CD34 和 SOX-18 表达。我们的结果表明,肿瘤细胞中的巢蛋白表达与表达巢蛋白、CD31、CD34 和 SOX-18 的血管面积和数量相关。我们还发现表达巢蛋白的血管与表达 SOX-18 的血管之间存在正相关。我们的结果与之前的研究结果一致,之前的研究表明,内皮细胞中的巢蛋白表达与三阴性亚型、分化较差的 G3 肿瘤、较高的增殖指数和较短的总生存期密切相关。还在代表不同肿瘤侵袭性水平和反映组织学分级的人乳腺癌细胞系(MCF-7、SK-BR-3、MDA-MB-231 和 BO2 细胞)中检查了巢蛋白表达。在更具侵袭性的 MDA-MB-231 和 BO2 细胞中观察到更高的巢蛋白蛋白水平,而在 MCF-7 和 SK-BR-3 细胞中则较低。

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