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中性粒细胞明胶酶相关脂质运载蛋白在癌症中的作用。

Neutrophil gelatinase-associated lipocalin in cancer.

出版信息

Adv Clin Chem. 2014;64:179-219. doi: 10.1016/b978-0-12-800263-6.00004-5.

DOI:10.1016/b978-0-12-800263-6.00004-5
PMID:24938019
Abstract

Neutrophil gelatinase-associated lipocalin (NGAL), also known as lipocalin-2, is a 178-amino acid protein which exists in three molecular forms, including a 25-kDa monomer, a 45-kDa homodimer, and a 135-kDa heterodimer complexed with matrix metalloproteinase 9 (MMP-9). Polymorphonuclear neutrophils and tubular cells of the kidney are the most representative cellular sources. As such, NGAL is now considered the biochemical gold standard for early diagnosis of acute kidney injury. Recent evidence suggests, however, that ectopic or enhanced expression of NGAL may occur in many other pathologic conditions including cancer. Several epidemiologic studies, as reviewed in this chapter, showed that a variety of malignant tumors consistently overexpressed NGAL with increased concentration in blood, urine, and other biologic fluids. In addition, NGAL was frequently associated with tumor size, stage, and invasiveness. These features thus make it a potential biomarker for malignancy. A number of experimental studies also demonstrated that the ability to bind MMP-9, to scavenge iron into cancer cells along with the effect on subcellular localization of transmembrane proteins such as cadherins and catenins, confers this protein the potential to enhance can cer aggressiveness and makes it an appealing target of future anticancer research.

摘要

中性粒细胞明胶酶相关脂质运载蛋白(NGAL),也称为脂质运载蛋白-2,是一种由 178 个氨基酸组成的蛋白质,存在三种分子形式,包括 25kDa 的单体、45kDa 的同源二聚体和与基质金属蛋白酶 9(MMP-9)结合的 135kDa 异源二聚体复合物。多形核白细胞和肾脏的管状细胞是最具代表性的细胞来源。因此,NGAL 现在被认为是急性肾损伤早期诊断的生化金标准。然而,最近的证据表明,NGAL 的异位或增强表达可能发生在许多其他病理状况中,包括癌症。本章中综述的几项流行病学研究表明,多种恶性肿瘤始终过度表达 NGAL,血液、尿液和其他生物液中的浓度增加。此外,NGAL 经常与肿瘤大小、分期和侵袭性相关。这些特征使其成为恶性肿瘤的潜在生物标志物。许多实验研究还表明,与 MMP-9 结合的能力、将铁摄取到癌细胞中以及对跨膜蛋白(如钙粘蛋白和连环蛋白)的亚细胞定位的影响,使这种蛋白质具有增强癌症侵袭性的潜力,并使其成为未来抗癌研究的一个有吸引力的靶点。

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