The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer.
The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer.
复制标题
DOI：
10.1016/j.bbcan.2012.03.008
复制
发表时间：
2012-08
影响因子：
11.2
通讯作者：
Batra, Surinder K.
中科院分区：
文献类型：
--
作者：
Chakraborty, Subhankar;Kaur, Sukhwinder;Guha, Sushovan;Batra, Surinder K.
中性粒细胞明胶酶相关脂质运载蛋白（NGAL），也称为癌基因24p3、子宫钙蛋白、铁载体蛋白或脂质运载蛋白2，是一种24 kDa的分泌型糖蛋白，最初从感染猴病毒40（SV - 40）的小鼠肾细胞培养物中纯化得到。后续研究表明，它是脂质运载蛋白家族的成员，该家族的蛋白质可转运小分子疏水性配体。从那时起，据报道NGAL在一些正常组织中表达，在这些组织中它起到抵御细菌感染和调节氧化应激的作用。它的表达在一些良性和恶性疾病中也失调。它体积小、可分泌且相对稳定，这使得它在包括炎症和癌症在内的许多疾病中被作为诊断和预后生物标志物进行研究。主要针对人NGAL的小鼠同源物脂质运载蛋白2（Lcn2）进行的功能研究表明，Lcn2对与细菌铁载体（铁结合蛋白）以及某些人类蛋白质（如去甲肾上腺素）络合的铁具有很强的亲和力。通过螯合含铁的铁载体，Lcn2剥夺了细菌的一种重要营养物质，从而抑制了它们的生长（抑菌作用）。在恶性细胞中，其提出的功能包括抑制细胞凋亡（在甲状腺癌细胞中）、侵袭和血管生成（在胰腺癌中）以及增加增殖和转移（在乳腺癌和结肠癌中）。在小鼠模型中，Lcn2的异位表达也促进BCR - ABL诱导的慢性粒细胞白血病。通过将铁转运进细胞和运出细胞，NGAL还调节铁反应基因。此外，它通过与蛋白水解酶基质金属蛋白酶 - 9（MMP - 9）形成复合物来稳定该酶，从而防止其自身降解。调节NGAL表达的因素众多，从白细胞介素、肿瘤坏死因子 - α和干扰素等促炎细胞因子到视黄酸等维生素。这篇综述文章的目的是研究NGAL的表达、结构、调节和生物学作用，并批判性地评估它作为人类良性和恶性疾病中一种新型诊断和预后标志物的潜力。
Neutrophil gelatinase associated lipocalin (NGAL), also known as oncogene 24p3, uterocalin, siderocalin or lipocalin 2, is a 24 kDa secreted glycoprotein originally purified from a culture of mouse kidney cells infected with simian virus 40 (SV-40). Subsequent investigations have revealed that it is a member of the lipocalin family of proteins that transport small, hydrophobic ligands. Since then, NGAL expression has been reported in several normal tissues where it serves to provide protection against bacterial infection and modulate oxidative stress. Its expression is also dysregulated in several benign and malignant diseases. Its small size, secreted nature and relative stability have led to it being investigated as a diagnostic and prognostic biomarker in numerous diseases including inflammation and cancer. Functional studies, conducted primarily on lipocalin 2 (Lcn2), the mouse homologue of human NGAL have revealed that Lcn2 has a strong affinity for iron complexed to both bacterial siderophores (iron binding proteins) and certain human proteins like norepinephrine. By sequestering iron-laden siderophores, Lcn2 deprives bacteria of a vital nutrient and thus inhibits their growth (bacteriostatic effect). In malignant cells, its proposed functions range from inhibiting apoptosis (in thyroid cancer cells), invasion and angiogenesis (in pancreatic cancer) to increasing proliferation and metastasis (in breast and colon cancer). Ectopic expression of Lcn2 also promotes BCR-ABL induced chronic myelogenous leukemia in murine models. By transporting iron into and out of the cell, NGAL also regulates iron responsive genes. Further, it stabilizes the proteolytic enzyme matrix metalloprotease-9 (MMP-9) by forming a complex with it, and thereby prevents its autodegradation. The factors regulating NGAL expression are numerous and range from pro-inflammatory cytokines like interleukins, tumor necrosis factor-α and interferons to vitamins like retinoic acid. The purpose of this review article is to examine the expression, structure, regulation and biological role of NGAL and critically assess its potential as a novel diagnostic and prognostic marker in both benign and malignant human diseases.
登录
查看更多内容
影响因子：
7.7
作者：
BALLARD, DJ;HUMPHREY, LL;PALUMBO, PJ
通讯作者：
PALUMBO, PJ
影响因子：
38.9
作者：
Bagshaw, Sean M.;Bennett, Michael;Bellomo, Rinaldo
通讯作者：
Bellomo, Rinaldo
影响因子：
3.5
作者：
Alam, NA;Rowan, AJ;Tomlinson, IPM
通讯作者：
Tomlinson, IPM
影响因子：
6
作者：
Aghel, Arash;Shrestha, Kevin;Mullens, Wilfried;Borowski, Allen;Tang, W. H. Wilson
通讯作者：
Tang, W. H. Wilson
影响因子：
2.8
作者：
Bachorzewska-Gajewska, H.;Malyszko, J.;Dobrzycki, S.
通讯作者：
Dobrzycki, S.