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原发性中枢神经系统淋巴瘤中单核细胞趋化蛋白1的表达与增殖

Monocyte chemoattractant protein 1 expression and proliferation in primary central nervous system lymphoma.

作者信息

Takahashi Yoshinobu, Sawada Takahiro, Akahane Toshiaki, Kawase Yumiko, Ikeda Hidetoshi, Makino Keishi, Nakamura Hideo, Hide Takuichiro, Yano Shigetoshi, Hashimoto Naoya, Kamada Hajime

机构信息

Department of Neurosurgery, Hokuto Hospital, Obihiro, Hokkaido 080-0033, Japan.

Department of Cancer Biology and Genetics, Hokuto Hospital, Obihiro, Hokkaido 080-0033, Japan.

出版信息

Oncol Lett. 2017 Jul;14(1):264-270. doi: 10.3892/ol.2017.6122. Epub 2017 May 4.

Abstract

Whether the poor prognosis of primary central nervous system lymphoma (PCNSL) compared with systemic diffuse large B cell lymphoma (DLBCL) is attributable to the immune privilege of the intracerebral location or to intrinsic differences in the biological characteristics of two types of lymphoma remains unclear. Monocyte chemoattractant protein 1 (MCP-1) is essential to support tumor cell survival and growth, and the present study aimed to compare MCP-1 expression in PCNSL and peripheral DLBCL. The present study included 19 patients with PCNSL and 16 patients with DLBCL, all of whom had tissue diagnosis and lymphoma tissue samples available for analysis. Histology included immunohistochemistry using antibodies against a panel of lymphoma markers, antibodies specific to MCP-1, and antibodies specific to tumor-associated macrophages. MCP-1 expression was quantified using immunostaining scoring. RNA extraction and reverse transcription-quantitative polymerase chain reaction were used to determine mRNA expression. In addition, a human brain-derived lymphoma cell line, HKBML, was stimulated with MCP-1 and cell proliferation was measured by 5-bromo-2'-deoxyuridine incorporation. The expression levels of mRNA and MCP-1 protein were significantly increased in PCNSL compared with peripheral DLBCL. MCP-1 induced tyrosine phosphorylation of mitogen-activated protein kinase in HKBML cells, as analyzed by western blotting. The results of the present study indicated that MCP-1 expression in PCNSL promoted cell proliferation in an autocrine manner.

摘要

与系统性弥漫性大B细胞淋巴瘤(DLBCL)相比,原发性中枢神经系统淋巴瘤(PCNSL)预后较差,这是由于脑内位置的免疫特权还是两种淋巴瘤生物学特性的内在差异所致,目前尚不清楚。单核细胞趋化蛋白1(MCP-1)对支持肿瘤细胞的存活和生长至关重要,本研究旨在比较PCNSL和外周DLBCL中MCP-1的表达情况。本研究纳入了19例PCNSL患者和16例DLBCL患者,所有患者均有组织诊断且有淋巴瘤组织样本可供分析。组织学检查包括使用一组淋巴瘤标志物抗体、MCP-1特异性抗体和肿瘤相关巨噬细胞特异性抗体进行免疫组织化学检测。使用免疫染色评分对MCP-1表达进行定量。采用RNA提取和逆转录定量聚合酶链反应来测定mRNA表达。此外,用人脑来源的淋巴瘤细胞系HKBML用MCP-1刺激,并通过5-溴-2'-脱氧尿苷掺入法测量细胞增殖。与外周DLBCL相比,PCNSL中mRNA和MCP-1蛋白的表达水平显著升高。通过蛋白质印迹分析,MCP-1诱导了HKBML细胞中丝裂原活化蛋白激酶的酪氨酸磷酸化。本研究结果表明,PCNSL中MCP-1的表达以自分泌方式促进细胞增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e3/5494900/3afeeaf174d4/ol-14-01-0264-g00.jpg

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