title: Anti-angiogenic and tumor-suppressive roles of candidate tumor-suppressor gene, Fibulin-2, in nasopharyngeal carcinoma.
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.
authors: Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong (SAR), PR China.
authors: E W L
authors: EW
authors: Law
authors: A K L
authors: AK
authors: Cheung
authors: V I
authors: VI
authors: Kashuba
authors: T V
authors: TV
authors: Pavlova
authors: E R
authors: ER
authors: Zabarovsky
authors: H L
authors: HL
authors: Lung
authors: Y
authors: Y
authors: Cheng
authors: D
authors: D
authors: Chua
authors: D
authors: D
authors: Lai-Wan Kwong
authors: S W
authors: SW
authors: Tsao
authors: T
authors: T
authors: Sasaki
authors: E J
authors: EJ
authors: Stanbridge
authors: M L
authors: ML
authors: Lung
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019175:DNA Methylation; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D047368:Tumor Burden; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D020033:Protein Isoforms; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; C084612:fibulin 2; D020778:Matrix Metalloproteinase 2