Relation of LAT1/4F2hc expression with pathological grade, proliferation and angiogenesis in human gliomas.

Relation of LAT1/4F2hc expression with pathological grade, proliferation and angiogenesis in human gliomas.
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DOI:
10.1186/1472-6890-12-4
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发表时间:
2012-02-28
影响因子:
--
通讯作者:
Tamiya T
Tamiya T
中科院分区:
其他
文献类型:
--
作者:
Haining Z;Kawai N;Miyake K;Okada M;Okubo S;Zhang X;Fei Z;Tamiya T

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LAT 1/4F 2 hc异二聚体复合物是通过质膜转运大的中性必需氨基酸的主要途径。尽管已经证明LAT 1/4F 2 hc在包括胶质瘤在内的多种人类肿瘤中高度表达,并且LAT 1过表达与胶质瘤分级和胶质瘤患者的不良预后相关,但LAT 1/4F 2 hc在胶质瘤中的精确组织定位以及LAT 1/4F 2 hc在胶质瘤生物学特征中的精确作用仍不清楚。本研究应用免疫组化方法检测了62例人脑胶质瘤组织中LAT 1、4F 2 hc、CD 34和Ki-67的表达,并对LAT 1/4F 2 hc的表达水平、Ki-67的标记指数、细胞凋亡指数、细胞凋亡指数进行了分析。半定量检测Ki-67指数(Ki-67 LI)和微血管密度(MVD);进一步分析胶质瘤中LAT 1/4F 2 hc表达与组织病理学特征、Ki-67 LI及MVD的关系。结果表明,LAT 1和4F 2 hc在所有检测标本中均有表达。LAT 1和4F 2 hc的表达水平与胶质瘤的病理分级显著相关,两者的表达水平均与Ki-67指数显著相关。我们还发现,LAT 1和4F 2 hc的免疫反应,观察肿瘤细胞以及血管内皮细胞;此外,LAT 1的表达水平与胶质瘤MVD以及显着相关。LAT 1/4F 2 hc过表达与胶质瘤的恶性表型和增殖密切相关,LAT 1与胶质瘤血管生成有关。LAT 1/4F 2 hc,尤其是LAT 1,有可能成为胶质瘤生物治疗的新的潜在分子靶点。
LAT1/4F2hc heterodimeric complex is a major route for the transport of large neutral essential amino acids through the plasma membrane. Although it has been shown that LAT1/4F2hc is highly expressed in a variety of human tumors including gliomas, and LAT1 over-expression is associated with glioma grade and poor prognosis of glioma patients, the precise tissue location of LAT1/4F2hc in gliomas and the precise role of LAT1/4F2hc in glioma biological features remain unclear. In the current study, the expressions of LAT1, 4F2hc, CD34 and Ki-67 were investigated by immunohistochemistry in 62 cases of human brain glioma; LAT1/4F2hc expression level, Ki-67 labeling index (Ki-67 LI) and microvessel density (MVD) were measured semi-quantitatively; and the correlation of LAT1/4F2hc expression with histopathological features, Ki-67 LI and MVD in gliomas was further analyzed. The results showed that both LAT1 and 4F2hc were expressed in all examined specimens. LAT1 but 4F2hc expression levels significantly correlated with the pathological grade and both expression levels significantly correlated with Ki-67 LI of gliomas. We also demonstrated that both LAT1 and 4F2hc immunoreactivity were observed in tumor cells as well as vascular endothelia; furthermore, the LAT1 expression level was markedly associated with glioma MVD as well. LAT1/4F2hc over-expression is closely correlates with the malignant phenotype and proliferation of gliomas, and LAT1 was associates with glioma angiogenesis. LAT1/4F2hc, especially LAT1, may become a novel potential molecular target for glioma biological therapy.
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