Tenascin-C expression in the cyst wall and fluid of human brain tumors correlates with angiogenesis

Tenascin-C expression in the cyst wall and fluid of human brain tumors correlates with angiogenesis
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DOI:
10.1097/00006123-199711000-00007
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发表时间:
1997-11-01
期刊:
影响因子:
4.8
通讯作者:
Zagzag, D
Zagzag, D
中科院分区:
医学1区
文献类型:
--
作者:
Jallo, GI;Friedlander, DR;Zagzag, D

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目的:腱生蛋白C(Tenascin-C,TN)是一种细胞外基质糖蛋白。本研究的目的是确定脑肿瘤囊液中TN的浓度是否可以作为血管生成和胶质瘤Grade.METHODS的标志物:我们研究了TN的表达在人脑肿瘤的囊壁和囊液的免疫组化,免疫沉淀,免疫印迹。肿瘤包括12个星形细胞瘤(5例多形性胶质母细胞瘤,1例间变性星形细胞瘤,1例低度恶性星形细胞瘤,4例幼年毛细胞星形细胞瘤,1例混合性胶质瘤),2例胚胎发育不良性神经上皮瘤,3例颅咽管瘤,2例室管膜瘤,2例转移癌,3例蛛网膜囊肿,1例胶质室管膜囊肿,1例炎性囊肿。我们在室管膜瘤、颅咽管瘤和非毛细胞性低级别星形细胞瘤的囊液中没有检测到TN的表达。与此相反,TN检测到所有其他肿瘤的囊液。使用Phosphorlmager装置(分子动力学,加利福尼亚州桑尼维尔)进行定量免疫印迹的结果显示,平均而言,与间变性星形细胞瘤相比,在多形性胶质母细胞瘤肿瘤中观察到的信号高5倍,与混合性胶质瘤、幼年毛细胞星形细胞瘤和胚胎发育不良神经上皮肿瘤相比,信号高10倍。星形细胞瘤中TN免疫组化结果与胶质瘤分级相关,在高级别胶质瘤中观察到更强的增生血管和肿瘤细胞染色。在室管膜瘤、蛛网膜囊肿和缺乏增生血管的胶质室管膜囊肿的壁中未检测到TN免疫反应性,在颅咽管瘤的血管周围胶质边缘中观察到最小的TN免疫反应性。没有TN被检测到在这些囊性projects.CONCLUSION囊液中:TN的存在和周围的增生血管和肿瘤细胞存在于星形细胞瘤的囊壁和其沉积在瘤内囊液中,其中血管生成因子已被检测到进一步表明TN作为血管生成调制器的作用。这些初步结果表明,肿瘤囊液中TN的免疫检测可以指示肿瘤的类型和分级。
OBJECTIVE: Tenascin-C (TN) is an extracellular matrix glycoprotein with a characteristic six-armed structure. The aim of this study was to determine whether the concentration of TN in the cyst fluid of brain tumors can be used as a marker for angiogenesis and glioma grade.METHODS: We investigated the expression of TN in the cyst wall and cyst fluid of human brain tumors by immunohistochemistry, immunoprecipitation, and immunoblotting. The tumors included 12 astrocytomas (5 glioblastoma multiforme tumors, 1 anaplastic astrocytoma, 1 low-grade astrocytoma, 4 juvenile pilocytic astrocytomas, and 1 mixed glioma), 2 dysembryoplastic neuroepithelial tumors, 3 craniopharyngiomas, 2 ependymomas, 2 metastatic carcinomas, 3 arachnoid cysts, 1 glial ependymal cyst, and 1 inflammatory cyst.RESULTS: We detected no expression of TN in the cyst fluids of the ependymomas, craniopharyngiomas, and nonpilocytic low-grade astrocytoma. By contrast, TN was detected in the cyst fluids of all the other tumors. Results of quantitative immunoblotting using a Phosphorlmager unit (Molecular Dynamics, Sunnyvale, CA) revealed that, on average, a 5-fold higher signal was observed in the glioblastoma multiforme tumors as compared with the anaplastic astrocytoma, and a 10-fold higher signal as compared with the mixed glioma, juvenile pilocytic astrocytomas, and dysembryoplastic neuroepithelial tumors. Results of TN immunohistochemistry in the astrocytomas correlated with glioma grade, with stronger staining of the hyperplastic vessels and tumor cells being observed in higher grade gliomas. No TN immunoreactivity was detected in the walls of the ependymomas, arachnoid cysts, and glial ependymal cyst that lack hyperplastic vessels, and minimal TN immunoreactivity was observed in the perivascular gliotic rim of the craniopharyngiomas. No TN was detected in the cyst fluid of these cystic processes.CONCLUSION: The presence of TN in and around the hyperplastic vessels and tumor cells present in the cyst walls of astrocytomas and its deposition in the intratumoral cyst fluid in which angiogenic factors have been detected further suggests a role for TN as an angiogenic modulator. These preliminary results suggest that immunodetection of TN in the tumor cyst fluid may indicate tumor type and grade.