Kyurkchiev Dobroslav, Naydenov Emanuil, Tumangelova-Yuzeir Kalina, Ivanova-Todorova Ekaterina, Belemezova Kalina, Bochev Ivan, Minkin Krasimir, Mourdjeva Milena, Velikova Tsvetelina, Nachev Sevdalin, Kyurkchiev Stanimir
Department of Clinical Laboratory and Clinical Immunology, University Hospital "St. Ivan Rilski", Medical University Sofia, 15 "Acad. Ivan Geshov" Str., 1431, Sofia, Bulgaria,
Cell Mol Neurobiol. 2014 May;34(4):479-89. doi: 10.1007/s10571-014-0031-3. Epub 2014 Jan 29.
Glioblastoma multiforme (GBM) is the most common and malignant tumor in the central nervous system. One of the contemporary hypotheses postulates that its pathogenesis is associated with the cancer stem cells (CSCs) which originate from mutations in the normal neural stem cells residing in their specific "niches." Simultaneously with its aggressive development the tumor suppresses the local immune system by different secreted and/or cell expressed factors. Progesterone-induced blocking factor (PIBF) is an immunomodulatory protein with known role in the regulation of the immune response in the reproductive system. Expression of PIBF has been described in some tumors as one of the factors suppressing the anti-tumor immunity. The aim of the present study was to check for the expression of PIBF from cells isolated from six GBMs. To characterize the cultured cells and to study the PIBF expression confocal microscopy, flow cytometry, ELISA, and real-time PCR were used. The results obtained showed expression of markers typical for cancer CSCs and secretion of interleukin 6 by the GBM-derived cultured cells. The results convincingly prove that PIBF is intracellularly expressed by the cultured cells from the all six GBM samples, and this fact is confirmed by three different methods-flow cytometry, confocal microscopy, and real-time PCR. This paper reports for the first time the expression of PIBF by GBM-derived cells cultured in vitro and reveals a new aspect of the immunosuppressive mechanism used by GBM in escaping the immune control.
多形性胶质母细胞瘤(GBM)是中枢神经系统中最常见且恶性程度最高的肿瘤。当代的一种假说认为,其发病机制与癌症干细胞(CSC)有关,这些干细胞源自存在于其特定“微环境”中的正常神经干细胞的突变。在肿瘤侵袭性发展的同时,它通过不同的分泌因子和/或细胞表达因子抑制局部免疫系统。孕酮诱导阻断因子(PIBF)是一种免疫调节蛋白,在生殖系统免疫反应调节中具有已知作用。PIBF的表达在一些肿瘤中被描述为抑制抗肿瘤免疫的因素之一。本研究的目的是检测从六个GBM分离的细胞中PIBF的表达。为了表征培养的细胞并研究PIBF的表达,使用了共聚焦显微镜、流式细胞术、酶联免疫吸附测定(ELISA)和实时聚合酶链反应(PCR)。获得的结果显示,GBM来源的培养细胞表达癌症CSC的典型标志物并分泌白细胞介素6。结果令人信服地证明,PIBF在所有六个GBM样本的培养细胞中细胞内表达,这一事实通过三种不同方法得到证实——流式细胞术、共聚焦显微镜和实时PCR。本文首次报道了体外培养的GBM来源细胞中PIBF的表达,并揭示了GBM逃避免疫控制所采用的免疫抑制机制的一个新方面。