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

Oncogene volume 31, pages 728–738 (2012)Cite this article

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.

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Abbreviations

Dox:

doxycycline

ECM:

extracellular matrix

FBLN2S:

short fibulin-2 isoform

FBLN2:

fibulin-2

FBLN2L:

long fibulin-2 isoform

MCH:

microcell hybrid

MI:

methylation index

NPC:

nasopharyngeal carcinoma

Q–PCR:

quantitative RT–PCR

TSG:

tumor-suppressor gene

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Acknowledgements

This work was supported by University Grants Council Area of Excellence grant AoE/M-06/08 to MLL and the Swedish Cancer Society, the Swedish Research Council, the Swedish Institute, and Karolinska Institute to ERZ.

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Authors and Affiliations

  1. Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Pokfulam, Hong Kong (SAR), PR China

    E W L Law, A K L Cheung, H L Lung, Y Cheng, D Chua, D Lai-wan Kwong & M L Lung

  2. Department of Microbiology, Department of Clinical Science and Education, Tumor and Cell Biology, Sodersjukhuset, Karolinska Institute, Stockholm, Sweden

    V I Kashuba, T V Pavlova & E R Zabarovsky

  3. Laboratory of Structural and Functional Genomics, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia

    E R Zabarovsky

  4. Comprehensive Oncology Centre, Hong Kong Sanatorium and Hospital, Happy Valley, Hong Kong (SAR), PR China

    D Chua

  5. Department of Anatomy, University of Hong Kong, Pokfulam, Hong Kong (SAR), PR China

    S W Tsao

  6. Department of Experimental Medicine I, Nikolaus-Fiebiger Center of Molecular Medicine Friedrich-Alexander-University, Erlangen, Germany

    T Sasaki

  7. Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, USA

    E J Stanbridge

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  1. E W L Law
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Correspondence to M L Lung.

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Law, E., Cheung, A., Kashuba, V. et al. Anti-angiogenic and tumor-suppressive roles of candidate tumor-suppressor gene, Fibulin-2, in nasopharyngeal carcinoma. Oncogene 31, 728–738 (2012). https://doi.org/10.1038/onc.2011.272

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