Selective accumulation of hematoporphyrin derivative in glioma through proton-coupled folate transporter SLC46A1.

Selective accumulation of hematoporphyrin derivative in glioma through proton-coupled folate transporter SLC46A1.
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DOI:
10.3164/jcbn.13-87
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发表时间:
2014-01
影响因子:
2.4
通讯作者:
Matsumura A
Matsumura A
中科院分区:
医学4区
文献类型:
--
作者:
Takada T;Tamura M;Yamamoto T;Matsui H;Matsumura A

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肿瘤特异性卟啉积累的机制尚不清楚。为了探讨质子偶联叶酸转运蛋白SLC 46 A1在胶质瘤中的表达及其与肿瘤荧光强度的关系,我们采用免疫组化和逆转录-聚合酶链反应(RT-PCR)方法检测了24例胶质瘤手术标本中SLC 46 A1的表达。我们还通过RT-PCR检测了SLC 46 A1在胶质瘤细胞系中的表达。用酶标仪和荧光显微镜测定细胞对血卟啉衍生物的摄取。在这些实验中,我们使用了三种人恶性胶质瘤细胞系:U87、U251和T98 G。免疫组化结果显示,SLC 46 A1在各标本的恶性肿瘤病灶中均呈阳性表达。SLC 46 A1强阳性表达在IV级胶质瘤中占33%,III级胶质瘤中占22%,II级胶质瘤中占17%。RT-PCR检测4例恶性胶质瘤冰冻切片均表达SLC 46 A1 mRNA。在体外,U87显示出最少的SLC 46 A1表达,U251居中,而T98 G显示出最多的表达。血卟啉衍生物(HpD)细胞摄取量与SLC 46 A1表达相关。提示HpD在胶质瘤细胞中的积累与SLC 46 A1的功能有关,SLC 46 A1参与胶质瘤细胞的荧光机制。
The mechanism of tumor-specific porphyrin accumulation is not clear. We investigated the expression of proton-coupled folate transporter SLC46A1 in glioma and aimed to clarify the relationship between tumor fluorescence and SLC46A1 expression.We confirmed the expression of SLC46A1 in surgical specimens from 24 glioma patients by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). We also investigated SLC46A1 expression in glioma cell lines by RT-PCR. The cellular uptake of hematoporphyrin derivative in vitro was measured with a microplate reader and fluorescence microscope. In these experiments, we used three human malignant glioma cell lines: U87, U251 and T98G. Immunohistochemistry showed SLC46A1 positivity in the malignant tumor lesion of each specimen. Strong positive SLC46A1 expression was observed in 33% of grade IV, 22% of grade III and 17% of grade II gliomas. All four randomly obtained malignant glioma frozen sections expressed SLC46A1 mRNA by RT-PCR. In vitro, U87 showed the least SLC46A1 expression, U251 was intermediate, and T98G showed the most expression. The amount of hematoporphyrin derivative (HpD) cellular uptake correlated with SLC46A1 expression. These results suggest that the accumulation of HpD in glioma cells is related to SLC46A1 function and SLC46A1 is involved in the mechanism of glioma fluorescence.
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