Galectin-1: A link between tumor hypoxia and tumor immune privilege
Galectin-1: A link between tumor hypoxia and tumor immune privilege
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DOI：
10.1200/jco.2005.02.0206
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发表时间：
2005-12-10
影响因子：
45.3
通讯作者：
Koong, AC
中科院分区：
文献类型：
--
作者：
Le, QT;Shi, GY;Koong, AC
目的鉴定头颈部鳞状细胞癌（HNSCC）中一种新的15 kDa低氧诱导分泌蛋白，并探讨其在肿瘤恶性进展中的作用。方法采用表面增强激光解吸电离飞行时间质谱（SELDI-TOF-MS）和串联维斯技术，对FaDu细胞中一种新的低氧诱导分泌蛋白进行鉴定。我们使用免疫印迹，实时聚合酶链反应（PCR），酶联免疫吸附试验，以确认缺氧诱导的这种分泌蛋白半乳糖凝集素-1在细胞系和异种移植。我们对来自101名HNSCC患者的肿瘤组织进行半乳糖凝集素-1，CA IX（碳酸酐酶IX，缺氧标志物）和CD 3（T细胞标志物）染色。结果SELDI-TOF研究在15 kDa处产生了一个缺氧诱导的峰，经维斯分析证明是galectin-1。免疫印迹和PCR研究证实了在几种癌细胞系中缺氧增加了半乳糖凝集素-1的表达。与呼吸室内空气的小鼠相比，呼吸10%O-2的荷瘤严重联合免疫缺陷（SCID）小鼠的血浆半乳糖凝集素-1水平更高。在HNSCC患者中，半乳糖凝集素-1和CA IX染色之间存在显著相关性（P = .01），半乳糖凝集素-1和CD 3染色之间存在强负相关性（P = .01）。结论Galectin-1是一种新的缺氧调节蛋白，可作为HNSCC预后的标志物。这项研究提出了一种新的机制，缺氧如何通过调节调节免疫赦免的蛋白质的分泌来影响实体瘤的恶性进展和治疗反应。
Purpose To identify a 15-KDa novel hypoxia-induced secreted protein in head and neck squamous cell carcinomas (HNSCC) and to determine its role in malignant progression,Methods We used surf ace-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) and tandem VIS to identify a novel hypoxia-induced secreted protein in FaDu cells. We used immunoblots, real-time polymerase chain reaction (PCR), and enzyme-linked immunoabsorbent assay to confirm the hypoxic induction of this secreted protein as galectin-1 in cell lines and xenografts. We stained tumor tissues from 101 HNSCC patients for galectin-1, CA IX (carbonic anhydrase IX, a hypoxia marker) and CD3 (a T-cell marker). Expression of these markers was correlated to each other and to treatment outcomes.Results SELDI-TOF studies yielded a hypoxia-induced peak at 15 kDa that proved to be galectin-1 by VIS analysis. Immunoblots and PCR studies confirmed increased galectin-1 expression by hypoxia in several cancer cell lines. Plasma levels of galectin-1 were higher in tumor-bearing severe combined immunodeficiency (SCID) mice breathing 10% O-2 compared with mice breathing room air. In HNSCC patients, there was a significant correlation between galectin-1 and CA IX staining (P = .01) and a strong inverse correlation between galectin-1 and CD3 staining (P = .01). Expression of galectin-1 and CD3 were significant predictors for overall survival on multivariate analysis.Conclusion Galectin-1 is a novel hypoxia-regulated protein and a prognostic marker in HNSCC. This study presents a new mechanism on how hypoxia can affect the malignant progression and therapeutic response of solid tumors by regulating the secretion of proteins that modulate immune privilege.