Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong (SAR), PR China.
Oncogene. 2012 Feb 9;31(6):728-38. doi: 10.1038/onc.2011.272. Epub 2011 Jul 11.
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.
纤连蛋白-2（FBLN2）已被确定为鼻咽癌（NPC）的候选肿瘤抑制基因。它最初是通过染色体 3 NotI 基因组微阵列筛选发现的，在 NPC 中频繁缺失或甲基化。FBLN2 位于染色体 3p25.1 上，通过与细胞外基质（ECM）蛋白的重要相互作用与肿瘤的发生发展有关。FBLN2 编码两种同工型。短同工型（FBLN2S）在正常组织中表达丰富，但在 NPC 中显著下调，而长同工型（FBLN2L）在正常和肿瘤组织中均无法检测到或仅低水平表达。该 FBLN2S 的重新引入抑制了体外细胞增殖、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。FBLN2 相关的血管生成是通过同时下调血管内皮生长因子和基质金属蛋白酶 2 实现的。这项研究提供了令人信服的证据，表明 FBLN2S 在 NPC 中具有重要的肿瘤抑制和抗血管生成作用。
