Anti-angiogenic and tumor-suppressive roles of candidate tumor-suppressor gene, Fibulin-2, in nasopharyngeal carcinoma
Anti-angiogenic and tumor-suppressive roles of candidate tumor-suppressor gene, Fibulin-2, in nasopharyngeal carcinoma
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DOI：
10.1038/onc.2011.272
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发表时间：
2012-02-01
期刊：
影响因子：
8
通讯作者：
Lung, M. L.
中科院分区：
文献类型：
--
作者：
Law, E. W. L.;Cheung, A. K. L.;Lung, M. L.
Fibulin-2（FBLN 2）是鼻咽癌的候选抑癌基因。最初通过3号染色体NotI基因组微阵列筛选鉴定，它在NPC中显示频繁的缺失或甲基化。FBLN 2位于染色体3p25.1上，并通过其与细胞外基质（ECM）蛋白的重要相互作用与肿瘤发展相关。FBLN 2编码两种亚型。短同种型（FBLN 2S）在正常组织中大量表达，但在NPC中显著下调，而长同种型（FBLN 2L）在正常和肿瘤组织中要么检测不到，要么仅以低水平表达。重新引入FBLN 2S可抑制体外细胞增殖、迁移、侵袭和血管生成。此外，裸鼠体内研究表明其表达与肿瘤和血管生成抑制有关。FBLN 2相关的血管生成通过血管内皮生长因子和基质金属蛋白酶2的伴随下调发生。这项研究提供了令人信服的证据，FBLN 2S在NPC中具有重要的肿瘤抑制和抗血管生成作用。Oncogene（2012）31，728-738; doi：10.1038/onc.2011.272; 2011年7月11日在线发表
Fibulin-2 (FBLN2) has been identified as a candidate tumor-suppressor gene in nasopharyngeal carcinoma (NPC). Originally identified through a chromosome 3 NotI genomic microarray screen, it shows frequent deletion or methylation in NPC. FBLN2 is located on chromosome 3p25.1 and is associated with tumor development through its important interactions with the extracellular matrix (ECM) proteins. FBLN2 encodes two isoforms. The short isoform (FBLN2S) is expressed abundantly in normal tissues, but is dramatically downregulated in NPC, while the long isoform (FBLN2L) is either not detectable or is expressed only at low levels in both normal and tumor tissues. Reintroduction of this FBLN2S inhibited cell proliferation, migration, invasion and angiogenesis in vitro. Furthermore, in vivo studies in nude mice show its expression is associated with tumor and angiogenesis suppression. FBLN2-associated angiogenesis occurs via concomitant downregulation of vascular endothelial growth factor and matrix metalloproteinase 2. This study provides compelling evidence that FBLN2S has an important tumor-suppressive and anti-angiogenic role in NPC. Oncogene (2012) 31, 728-738; doi:10.1038/onc.2011.272; published online 11 July 2011