锌指蛋白Zfx在人脑胶质瘤中的表达与意义

背景与目的：X染色体耦联锌指蛋白（Zfx）是锌指蛋白超家族中的一员,是胚胎干细胞和成体干细胞自我更新的共同分子基础。本研究探讨Zfx在人脑胶质瘤中的表达及其与脑胶质瘤的发生和恶性程度的关系有待探讨。方法：收集52例经病理证实的脑胶质瘤肿瘤标本和8例正常脑组织标本,根据病理结果对脑胶质瘤标本进行分组,通过实时定量PCR、免疫组织化学和Westemblot等方法对标本中zfx的mRNA和蛋白表达进行检测,应用统计学方法对正常脑组织和不同恶性程度脑胶质瘤中Zfx的表达进行分析。结果：免疫组化染色结果显示,ZfX主要表达于细胞核。脑胶质瘤中Zfx的mRNA和蛋白表达均高于其在正常脑组织中的表达．在不同病理分级的脑胶质瘤中Zfx的表达水平有差异,Zfx的表达水平随脑胶质瘤的恶性程度增高而增高。结论：Zfx的mRNA和蛋白在脑胶质瘤中高表达,与脑胶质瘤的恶性程度呈正相关．它有可能是脑胶质瘤抗凋亡、恶性增殖的一个关键性的调控因子。     

胶质瘤干细胞的分离、培养及初步鉴定

目的:探讨人脑胶质瘤干细胞的培养和分离方法。方法:取9例脑胶质瘤患者的手术标本进行处理,采用B27培养基进行培养,碱性成纤维细胞生长因子和表皮生长因子刺激细胞扩增;应用免疫组织化学染色对培养的细胞及其分化的细胞进行鉴定。结果:9例标本中共有7例成功培养出肿瘤细胞球,培养条件下呈悬浮状态生长,形成肿瘤细胞球,免疫细胞化学检测显示肿瘤球细胞表达胶质瘤干细胞的标志物CD133和Nestin,诱导分化后的肿瘤球细胞可以表达成熟神经细胞的标志物GFAP和TU-20。结论:体外的培养条件下,可以从胶质瘤组织中培养出胶质瘤干细胞,为胶质瘤的深入研究奠定基础。     

人恶性胶质瘤干细胞的分离与鉴定

目的:从人恶性胶质瘤中分离并鉴定胶质瘤干细胞。方法:采用神经干细胞无血清培养方法,分离胶质瘤干细胞,免疫细胞化学法、有限梯度稀释实验、二代球体形成分析、流式细胞分析等方法对胶质瘤干细胞进行鉴定。结果:3例患者原代培养胶质瘤细胞中CD133 细胞分别为7.4%、2.8%和4.2%。每100个原代胶质瘤细胞中可形成1个左右的胶质瘤细胞球;胶质瘤细胞球细胞均表达神经干细胞标记CD133和Nestin,不表达分化标志GFAP和MAP2,少数细胞表达分化标记MBP。每100个原代胶质瘤细胞球体细胞可形成6.07±2.15个悬浮生长的二代胶质瘤细胞球,二代细胞球细胞表达CD133和Nestin。胶质瘤细胞球细胞分化后细胞多数表达GFAP,少数表达MAP2和MBP。胶质瘤球体干细胞的增殖较原代胶质瘤细胞慢。胶质瘤球体细胞1×103个时可成瘤,原代培养的胶质瘤细胞需1×107。结论:采用神经干细胞培养条件可以很简便的分离出悬浮生长的胶质瘤球体干细胞。分离出的胶质瘤球体干细胞表达CD133抗原,具备肿瘤干细胞的基本特征。     

癌睾丸抗原OY-TES-1在脑胶质瘤中的表达及其抗体血清学分析

背景与目的:胶质瘤是最常见的原发性恶性脑肿瘤,预后差,生存率低.近年来,以利用癌睾丸(cancer-testis,CT)抗原作为靶抗原行肿瘤免疫治疗已成为研究的热点,而OY-TES-1是CT抗原家族中的一员.本研究拟了解OY-TES-1在脑胶质瘤中的mRNA表达及其抗体出现情况,探讨将OY-TES-1应用于肿瘤免疫治疗及辅助诊断的可能性.方法:收集51例脑胶质瘤患者肿瘤组织标本及配套血清,107例健康人血清.通过RT-PGR,从mRNA水平研究OY-TES-1在脑胶质瘤组织中的表达:用酶联免疫吸附分析技术(enzyme linked immunosorbent assay,ELISA)检测患者及健康人血清OY-TES-1抗体;同时对OY-TES-1 mRNA的表达及血清抗体出现的临床意义做初步分析.结果:在脑胶质瘤患者中OY-TES-1 mRNA阳性率为80.4％(41/51),血清OY-TES-1抗体阳性率为15.7％(8/51),健康人血清则为阴性.OY-TES-1 mRNA的表达和血清抗体的出现均与脑胶质瘤患者的年龄、性别、病理分级、肿瘤大小等临床指标无关.结论:OY-TES-1在脑胶质瘤中存在较高的表达,并能引起部分患者的体液免疫反应,有望作为胶质瘤免疫治疗的靶抗原.     

人脑胶质瘤组织培养的干细胞样细胞具有体外高侵袭能力

目的:分离培养人脑胶质瘤干细胞样细胞(glioma stem-like cell,GSLC),研究其体外侵袭力。方法:选取中国医科大学第一医院神经外科2008年10月至2009年1月间住院患者手术切除的脑胶质瘤组织8例,以无血清成球培养法培养胶质瘤细胞球;免疫细胞化学实验检测其CD133的表达;荧光免疫显微镜观察其分化后胶质细胞标志物GFAP和神经元标志物TU-20的表达;matrigel侵袭实验检测其侵袭力,并与原代脑胶质瘤细胞进行比较。结果:成功分离培养出人脑胶质瘤细胞球细胞,该细胞表达干细胞标志物CD133;能自我更新与增殖;诱导分化后,GFAP和TU-20均为阳性表达,提示其为GSLC。胶质瘤细胞球细胞侵袭细胞数显著多于原代胶质瘤细胞[(261.23±87.20)vs(116.08±63.88)个,P<0.01];此外,胶质瘤细胞球细胞穿过matrigel胶后可再次聚集成球状生长。结论:成功分离培养人脑胶质瘤组织中的GSLC,其体外具有较高的侵袭力,可能参与脑胶质瘤的侵袭和转移。     

TGF-β2通过基质金属蛋白酶通路影响胶质瘤干细胞的侵袭能力

目的： 研究TGF-β2对胶质瘤干细胞侵袭能力的影响及其可能机制。 方法： 收集2016年4月至2017年4月中国医科 大学附属第一医院神经外科手术切除的8例人多形性成胶质细胞瘤组织标本,通过胰蛋白酶消化法进行胶质瘤细胞原代培养,部 分胶质瘤细胞加入含有EGF、bFGF、B27的DEME/F12培养基中进行无血清培养获得悬浮生长的肿瘤细胞球,免疫荧光染色及分 化实验验证肿瘤球是否为胶质瘤干细胞。ELISA方法检测胶质瘤干细胞分泌TGF-β2的水平,转染TGF-β2 siRNA后应用Tran- swell方法检测TGF-β2对胶质瘤侵袭能力影响,Western blotting检测TGF-β2对胶质瘤干细胞中基质金属蛋白酶（matrix metallo- proteinase,MMP）表达影响。 结果： 通过免疫荧光染色及分化实验证明原代培养的悬浮生长肿瘤细胞球为胶质瘤干细胞,肿瘤 细胞球表达CD133,在含血清培养基中可以分化为神经元和胶质细胞。胶质瘤干细胞比原代培养的胶质瘤 TGF-β2 分泌水平 明显升高[(74.13±3.63) vs (46.13±2.61) pg/ml, P<0.05]。沉默 TGF-β2 可以降低胶质瘤干细胞侵袭细胞数[(105.71±8.69) vs (63.67±5.93)个,P<0.05],并抑制MMP-2和MMP-9表达（均P<0.05）。 结论： TGF-β2 通过 MMP-2 和 MMP-9 通路增强胶质瘤 干细胞的侵袭能力。     

免疫磁珠法分选人脑胶质瘤干细胞及其培养和鉴定

背景与目的:脑胶质瘤治疗效果一直不理想,这与胶质瘤细胞无限增殖能力和侵袭性生长有关,本研究旨在从人脑胶质瘤组织和细胞株中分离脑胶质瘤干细胞、进行体外培养并对其干细胞特性加以鉴定。方法:采用以CD133为标志的免疫磁珠法从人脑胶质瘤组织和细胞株中分离脑胶质瘤干细胞并进行体外培养,通过免疫荧光技术检测干细胞标志物CD133、Nestin,诱导分化后检查分化细胞标志物MAP2、GFAP、MBP以及电镜超微结构观察和移植SCID鼠致瘤实验,对其干细胞特性加以鉴定。结果:新鲜人脑胶质瘤组织和胶质瘤细胞株中存在一小部分CD133 的胶质瘤细胞,能表达干细胞的标志物CD133和Nestin,符合干细胞的超微结构特点,体外培养能连续传代;诱导分化后能产生MAP2、GFAP、MBP染色阳性的细胞;移植SCID鼠后能形成与亲本肿瘤表型一致的移植瘤。结论:新鲜人脑胶质瘤组织和胶质瘤细胞株中存在的一小部分CD133 胶质瘤细胞具有干细胞的属性,就是胶质瘤中的肿瘤干细胞,即胶质瘤干细胞。     

SliTrk5在脑胶质瘤组织中的表达及临床意义

目的:检测SliTrk家族成员SliTrk5在脑胶质瘤组织中的表达,并探讨其在脑胶质瘤组织与正常脑组织中SliTrk5的表达差异,分析其与脑胶质瘤临床病理特征的关系。方法:收集96例脑组织标本,包含6例正常脑组织和90例脑胶质瘤组织,采用免疫组织化学染色及Western blot检测SliTrk5的蛋白表达水平,分析SliTrk5表达与脑胶质瘤临床病理特征的关系,同时进行RT-PCR检测SliTrk5在脑胶质瘤中的mRNA水平。结果:免疫组化结果显示,脑胶质瘤组织中SliTrk5表达较正常脑组织明显上调,差异具有统计学意义（P<0.05）。Western blot和RT-PCR的检测结果与免疫组化一致。根据不同病理特征比较高表达与低表达例数发现,SliTrk5在脑胶质瘤组织中的高表达与患者病理分级显著相关（P<0.05）。结论:SliTrk5在脑胶质瘤组织中异常表达,并与病理分级相关。     

人脑胶质瘤中PHLPP1的表达及意义

目的:研究PHLPP1在人脑胶质瘤组织中的表达及其临床意义。方法:选取徐州医学院附属医院神经外科2009年12月至2011年10月间手术切除并经病理证实的人脑胶质瘤标本37例,其中I级1例,Ⅱ级12例,Ⅲ级16例,胶质母细胞瘤8例。另取11例因脑创伤行内减压术患者的正常脑组织标本作为对照。应用RT-PCR、Western blotting分别检测各标本中PHLPP1 mRNA和PHLPP1蛋白的表达。结果:RT-PCR和Western-blotting检测结果显示正常脑组织标本中PHLPP1 mRNA和PHLPP1蛋白表达最高,不同级别胶质瘤组织PHLPP1 mRNA和PHLPP1蛋白表达差异有统计学意义(P<0.05),且随着肿瘤病理级别的增高,胶质瘤组织中PHLPP1 mRNA和PHLPP1蛋白表达值降低,表达差异有统计学意义(P<0.05)。结论:PHLPP1在正常脑组织和不同级别的脑胶质瘤组织中都有表达,其表达值与肿瘤的病理分级呈负相关性,这可能是胶质瘤发生发展的重要机制之一。     

Pygo2在脑胶质瘤组织和细胞的表达及临床意义

目的:检测Pygo2在脑胶质瘤组织和细胞中的表达,并探讨其临床意义.方法:采用RT-PCR检测5种胶质瘤细胞株Pygo2 mRNA表达,Real-timePCR检测67例Ⅱ～Ⅳ级脑胶质瘤组织中Pygo2 mRNA表达,免疫组织化学SP法检测80例脑胶质瘤组织中Pygo2的蛋白表达.结果:Pygo2 mRNA在5种胶质瘤细胞株中均有表达,其中U251细胞中最高,C6细胞中最低.Pygo2mRNA在正常脑组织中表达极低,而在脑胶质瘤Ⅱ～Ⅳ级表达显著增高,且Pygo2mRNA表达随肿瘤分级的增高而显著增强(P＜0.05).Pygo2在脑胶质瘤组织细胞中定位于胞核,在正常脑组织中表达呈阴性,而在脑胶质瘤组织中约有65.0%阳性表达,两者差异显著(P＜0.01).Pygo2表达Ⅱ级(WHOⅡ)中低,Ⅳ级(WHO Ⅳ)中高.Pygo2在脑胶质瘤Ⅰ级、Ⅱ级、Ⅲ级、Ⅳ级中表达阳性率分别是5/13(38.5%)、12/26(46.2%)、15/19(78.9%)、20/22(90.9%),Pygo2蛋白表达与肿瘤分级密切相关(P＜0.01).此外,Pygo2蛋白表达水平与患者的性别、年龄均无显著性差异(P＞0.05).结论:Pygo2在正常脑组织中呈阴性,在脑胶质瘤组织和细胞中均高表达,且在组织中其表达随胶质瘤级别增高而显著增强,提示Pygo2可能在脑胶质瘤的发生、恶性演进中起了重要作用.     

Fas-induced expression of chemokines in human glioma cells: involvement of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase

Fas transduces not only apoptotic signals through various pathways but also angiogenic and proinflammatory responses in vivo. Human glioma cells express Fas although sensitivity to Fas-mediated cell death is variable, suggesting that Fas may have functions other than apoptosis in these cells. In this study, we addressed alternative functions of Fas expressed on human gliomas by Fas ligation in three human glioma cell lines, CRT-MG, U373-MG, and U87-MG, and the in vivo expression of Fas and chemokines in human glioblastoma multiforme (GBM). Herein, we demonstrate that: (a) stimulation with agonistic anti-Fas monoclonal antibody CH-11 and human recombinant soluble Fas ligand induces expression of the CC chemokine MCP-1 and the CXC chemokine interleukin-8 by human glioma cell lines at the mRNA and protein levels in a dose- and time-dependent manner; (b) selective pharmacological inhibitors of MEK1 (U0126 and PD98059) and p38 mitogen-activated protein kinase (MAPK) (SB202190) suppress Fas-mediated chemokine expression in a dose-dependent manner; (c) Fas ligation on human glioma cells leads to activation of both extracellular signal-regulated kinases ERK1/ERK2 and p38 MAPK; and (d) GBM samples express higher levels of Fas compared with normal control brain, which correlates with increased interleukin 8 expression. These findings indicate that Fas ligation on human glioma cells leads to the selective induction of chemokine expression, which involves the ERK1/ERK2 and p38 MAPK signaling pathways. Therefore, the Fas-Fas ligand system in human brain tumors may be involved not only in apoptotic processes but also in the provocation of angiogenic and proinflammatory responses.     

Expression of NANOG in human gliomas and its relationship with undifferentiated glioma cells

Stemness genes, including NANOG, which have been reported to play a significant role in embryonic stem cells (ESCs), are purported to be expressed in specific human tumor types. In the present study, we explored the expression of NANOG in gliomas to demonstrate its key roles in maintaining the undifferentiated state of glioma cells. Brain tumor stem cells (BTSCs) were isolated from the human glioma cell line U87 and cultured in simplified serum-free medium. Significantly higher NANOG mRNA and protein expression levels were demonstrated in U87 parental attached cells and suspended BTSCs as well as in 69 glioma specimens of different pathological grades. The relative levels of NANOG mRNA and protein expression were higher in the BTSCs as compared to those in the U87 parental attached cells and were significantly positively correlated with pathological grade. The coexpression and relationship of NANOG, CD133 and GFAP in situ in the cellular levels was determined through double-label immunohistochemical staining in the gliomas. A positive correlation of NANOG and CD133 expression with pathological grade of the samples was noted, while NANOG and GFAP expression correlated negatively with the pathological grade (P<0.01). Overexpression of NANOG in gliomas and its close relationship with the undifferentiated state of glioma cells in?vivo and in vitro indicated that NANOG may contribute to the existence of BTSCs and may be related to tumorigenesis of the cerebrum by maintaining the undifferentiated state of glioma cells, which provides a foundation to further explore its role in the biological behavior of gliomas.     

Co-transduction of p27Kip1 strongly augments Fas ligand- and caspase-8-mediated apoptosis in U-373MG glioma cells

BACKGROUND: p27Kip1 is a potential tumor suppressor gene. As malignant gliomas express Fas at high levels, the relationship between Fas-mediated apoptosis and p27Kip1 expression may improve therapeutic approaches for treating gliomas. MATERIALS AND METHODS: In this study, we transduced U-373MG glioma cells with the Fas ligand or caspase-8 genes using adenovirus vectors after transduction of the p27Kip1 gene to induce cell cycle arrest in U-373MG cells, and evaluated the degree of apoptosis. RESULTS: The results demonstrate that expression of p27Kip1 enhanced Fas ligand- or caspase-8-mediated apoptosis in U-373MG cells. Expression of apoptosis-related genes such as Bax, Bcl-X(L), Bcl-2 or caspase-8 were reduced by p27Kip1 transduction compared with that of beta-actin, whereas p27Kip1 transduction did not affect the expression level of Fas or the Fas ligand. CONCLUSION: Combined transduction of p27Kip1 with Fas ligand or caspase-8 would overide the resistance mechanism to apoptosis in malignant gliomas.     

IFN-β基因诱导裸鼠胶质瘤Fas 表达上调及细胞凋亡的实验研究

 目的 研究β干扰素基因对人脑胶质瘤的诱导凋亡作用,以及能否诱导胶质瘤细胞Fas表达上调,并探讨了β干扰素基因诱导细胞凋亡及Fas表达上调之间的联系. 方法 建立裸鼠SHG44胶质瘤模型,用脂质体包埋法将IFN-β基因的真核表达载体pSV2IFNβ注入裸鼠皮下SHG44脑胶质瘤,观察肿瘤生长情况并计算肿瘤体积,通过免疫组化、TUNEL染色,了解IFN-β基因诱导人脑胶质瘤细胞凋亡的作用以及胶质瘤细胞Fas表达情况. 结果 IFN-β在荷瘤裸鼠瘤体内获得表达,裸鼠皮下胶质瘤生长受到抑制,并诱导SHG44胶质瘤细胞凋亡,胶质瘤细胞Fas表达明显高于对照组. 结论 IFN-β基因能够抑制人脑胶质瘤生长,并诱导胶质瘤细胞凋亡;IFN-β基因诱导胶质瘤细胞凋亡可能是Fas表达上调的结果.     

周期蛋白依赖性激酶1在胶质瘤组织中的表达及其沉默对胶质瘤细胞恶性表型的影响

目的探讨周期蛋白依赖性激酶1(CDK1)在胶质瘤组织中的表达及其沉默对胶质瘤细胞恶性表型的影响。方法利用自建的人脑胶质瘤体外细胞系SHG44及其移植瘤组织、脑肿瘤干细胞、神经干细胞、不同恶性程度的胶质瘤手术标本构建组织芯片,免疫组化染色检测其CDK1蛋白表达;应用RNA干扰技术使CDK1在SHG44细胞及其移植瘤组织中沉默,观察其随后发生的表型变化。结果CDK1在临床标本中随胶质瘤恶性程度升高表达强度增加,Ⅰ-Ⅳ级的阳性表达率分别为22.2%、40.0%、69.6%和78.6%(P=0.01)。体外培养的人脑胶质瘤SHG44细胞球体和裸小鼠皮下移植瘤CDK1表达强度均较高,而神经干细胞和脑肿瘤干细胞球体表达强度低,在细胞增殖活性高的人胚胎脑组织和裸小鼠骨髓中CDK1亦高表达,但在正常成人脑组织低表达。C1和C3体外转染SHG44细胞后,将细胞周期阻滞在G2/M期,而且诱导了凋亡,细胞凋亡率分别上升至27.8%和36.5%。CDK1沉默的裸鼠皮下移植瘤瘤重明显降低,细胞凋亡率为57.1%,明显高于对照组(8.5%)。结论CDK1的高表达呵促进胶质瘤的发生和发展,CDK1沉默后的肿瘤细胞恶性表型可得到控制,CDK1可作为胶质瘤病因分子行进一步研究。     

ABCG2在胶质瘤组织中的表达及意义

背景与目的:三磷酸腺苷结合盒转运体成员ABCG2(ATP-binding cassette superfamily G member 2)是源于造血干细胞的标志物之一,其在神经胶质瘤发生发展相关组织和细胞中的表达情况还不清楚.本研究检测ABCG2在不同恶性程度人脑胶质瘤组织标本、裸小鼠移植瘤标本、体外细胞系球体和胶质瘤干细胞球体中的表达情况并分析其意义.方法:制作布有不同恶性程度人脑胶质瘤组织标本、裸小鼠移植瘤标本、体外细胞系球体和胶质瘤干细胞球体等的组织芯片,用免疫组化方法检测ABCG2在组织芯片中的表达情况.结果:在71例人脑胶质瘤组织标本中ABCG2的阳性率为26.8%,其中Ⅰ级11.1%,Ⅱ级8.0%,Ⅲ级43.5%,Ⅳ级42.9%;Ⅰ～Ⅱ级与Ⅲ～Ⅳ级相比差异具有统计学意义(X2=10.710,P=0.001).在神经干细胞、裸小鼠移植瘤、胶质瘤干细胞球体表达率为100%.在多种正常组织中亦有不同程度的表达.在胶质瘤临床标本中ABCG2阳性细胞呈亲血管分布.结论:ABCG2在胶质瘤干细胞、恶性程度高的胶质瘤组织标本和移植瘤组织中高表达,并且呈亲血管分布.     

MicroRNA-183 upregulates HIF-1α by targeting isocitrate dehydrogenase 2 (IDH2) in glioma cells

MicroRNAs (miRs) are small, non-coding RNAs that regulate gene expression and contribute to cell proliferation, differentiation and metabolism. Our previous study revealed the extensive modulation of a set of miRs in malignant glioma. In that study, miR microarray analysis demonstrated the upregulation of microRNA-183 (miR-183) in glioblastomas. Therefore, we examined the expression levels of miR-183 in various types of gliomas and the association of miR-183 with isocitrate dehydrogenase 2 (IDH2), which has complementary sequences to miR-183 in its 3′-untranslated region (3′UTR). In present study, we used real-time PCR analysis to demonstrate that miR-183 is upregulated in the majority of high-grade gliomas and glioma cell lines compared with peripheral, non-tumorous brain tissue. The mRNA and protein expression levels of IDH2 are downregulated via the overexpression of miR-183 mimic RNA in glioma cells. Additionally, IDH2 mRNA expression is upregulated in glioma cells expressing anti-miR-183. We verified that miR-183 directly affects IDH2 mRNA levels in glioma cells using luciferase assays. In malignant glioma specimens, the expression levels of IDH2 were lower in tumors than in the peripheral, non-tumorous brain tissues. HIF-1α levels were upregulated in glioma cells following transfection with miR-183 mimic RNA or IDH2 siRNA. Moreover, vascular endothelial growth factor and glucose transporter 1, which are downstream molecules of HIF-1α, were upregulated in cells transfected with miR-183 mimic RNA. These results suggest that miR-183 upregulation in malignant gliomas induces HIF-1α expression by targeting IDH2 and may play a role in glioma biology.     

Expression of emmprin (CD147), a cell surface inducer of matrix metalloproteinases, in normal human brain and gliomas

EMMPRIN (extracellular matrix metalloproteinase inducer), also called CD147, basigin or M6 in the human, is a member of the immunoglobulin superfamily that is present on the surface of tumor cells and stimulates adjacent fibroblasts to produce matrix metalloproteinases (MMPs). In our study, we investigated expression of EMMPRIN in human normal brain and gliomas, since mouse basigin and chicken HT7, the species homologues of human EMMPRIN, are associated with neuronal interactions and normal blood-brain barrier function, respectively. EMMPRIN expression was detected in all samples of non-neoplastic brain and glioma tissues examined. However, expression levels of EMMPRIN mRNA and protein were significantly higher in gliomas than in non-neoplastic brain. Moreover, levels of mRNA expression and immunohistochemical staining correlated with tumor progression in gliomas: They were highest in the most malignant form of glioma, glioblastoma multiforme, followed by anaplastic astrocytoma and then low-grade astrocytoma. Also, immunolocalization revealed quite different distributions in non-neoplastic brain and glioma: EMMPRIN was demonstrated only in vascular endothelium in non-neoplastic regions of the brain, whereas it was present in tumor cells but not in proliferating blood vessels in malignant gliomas. These data indicate that an MMP inducer molecule EMMPRIN is differently expressed in human normal brain and gliomas and could be associated with astrocytoma progression. Possible mechanisms whereby glioma cell EMMPRIN could influence tumor progression will be discussed.