Anti-angiogenic and tumor-suppressive roles of candidate tumor-suppressor gene, Fibulin-2, in nasopharyngeal carcinoma

E W L Law, A K L Cheung, V I Kashuba, T V Pavlova, E R Zabarovsky, H L Lung, Y Cheng, D Chua, D Lai Wan Kwong, S W Tsao, T Sasaki, E J Stanbridge, M L Lung*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

81 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)728-738
Number of pages11
JournalOncogene
Volume31
Issue number6
Early online date11 Jul 2011
DOIs
Publication statusPublished - 9 Feb 2012

Scopus Subject Areas

  • Molecular Biology
  • Genetics
  • Cancer Research

User-Defined Keywords

  • anti-angiogenic
  • fibulin-2
  • methylation
  • nasopharyngeal carcinoma
  • tumor suppressor
  • VEGF

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