Department of Neurosurgery, Klinikum der Ludwig-Maximilians-Universität München, Campus Grosshadern, Munich, Germany.
PLoS One. 2012;7(1):e30429. doi: 10.1371/journal.pone.0030429. Epub 2012 Jan 19.
Krüppel-like factor 8 (KLF8) has only recently been identified to be involved in tumor cell proliferation and invasion of several different tumor entities like renal cell carcinoma, hepatocellular carcinoma and breast cancer. In the present study, we show for the first time the expression of KLF8 in gliomas of different WHO grades and its functional impact on glioma cell proliferation. In order to get information about KLF8-mRNA regulation qPCR was performed and did not reveal any significant difference in samples (n = 10 each) of non-neoplastic brain (NNB), low-grade gliomas (LGG, WHO°II) and glioblastomas (GBM, WHO°IV). Immunohistochemistry of tissue samples (n = 7 LGG, 11 AA and 12 GBM) did not show any significant difference in the fraction of KLF8-immunopositive cells of all analyzed cells in LGG (87%), AA (80%) or GBM (89%). Tissue samples from cerebral breast cancer metastasis, meningiomas but also non-neoplastic brain demonstrated comparable relative cell counts as well. Moreover, there was no correlation between KLF8 expression and the expression pattern of the assumed proliferation marker Ki67, which showed high variability between different tumor grade (9% (LGG), 6% (AA) and 15% (GBM) of Ki67-immunopositive cells). Densitometric analysis of Western blotting revealed that the relative amount of KLF8-protein did also not differ between the highly aggressive and proliferative GBM (1.05) compared to LGG (0.93; p<0.05, studens t-test). As demonstrated for some other non-glial cancer entities, KLF8-knockdown by shRNA in U87-MG cells confirmed its functional relevance, leading to an almost complete loss of tumor cell proliferation. Selective blocking of KLF8 might represent a novel anti-proliferative treatment strategy for malignant gliomas. Yet, its simultaneous expression in non-proliferating tissues could hamper this approach.
Krüppel 样因子 8(KLF8)最近才被确定参与多种不同肿瘤实体的肿瘤细胞增殖和侵袭,如肾细胞癌、肝细胞癌和乳腺癌。在本研究中,我们首次展示了 KLF8 在不同 WHO 分级的脑胶质瘤中的表达及其对胶质瘤细胞增殖的功能影响。为了获取 KLF8-mRNA 调节的信息,我们进行了 qPCR 实验,但在非肿瘤性脑(NNB)、低级别胶质瘤(LGG,WHO°II)和胶质母细胞瘤(GBM,WHO°IV)样本(每组各 10 例)中没有发现明显差异。组织样本(n=7 例 LGG、11 例 AA 和 12 例 GBM)的免疫组化分析显示,在 LGG(87%)、AA(80%)或 GBM(89%)的所有分析细胞中,KLF8 免疫阳性细胞的比例没有明显差异。脑乳腺癌转移、脑膜瘤和非肿瘤性脑的组织样本也显示出类似的相对细胞计数。此外,KLF8 表达与假定的增殖标志物 Ki67 的表达模式之间没有相关性,Ki67 在不同肿瘤分级之间表现出很高的变异性(LGG 为 9%,AA 为 6%,GBM 为 15%)。Western blot 的密度分析显示,与高度侵袭性和增殖性的 GBM(1.05)相比,KLF8 蛋白的相对量在 LGG 中也没有差异(0.93;p<0.05,学生 t 检验)。与一些其他非神经胶质瘤实体一样,U87-MG 细胞中 KLF8 的 shRNA 敲低证实了其功能相关性,导致肿瘤细胞增殖几乎完全丧失。选择性阻断 KLF8 可能成为恶性脑胶质瘤的一种新的抗增殖治疗策略。然而,其在非增殖组织中的同时表达可能会阻碍这种方法。