May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Depsipeptide (DP), Histone Deacetylase Inhibitor (HDACI), Inhibits Migration of Primary and Metastatic Uveal Melanoma (UM) Cells by Down-regulation of Matrix Metalloproteinase (MMP) 2 and 9 Gene Expression
Author Affiliations & Notes
  • M.I. Klisovic
    Ophthalmology, Ohio State University, Columbus, OH, United States
  • D.D. Klisovic
    Ophthalmology, Ohio State University, Columbus, OH, United States
  • S.E. Katz
    Ophthalmology, Ohio State University, Columbus, OH, United States
  • D. Effron
    Ophthalmology, Ohio State University, Columbus, OH, United States
  • G. Marcucci
    Internal Medicine, Ohio State University, Columbus, OH, United States
  • Footnotes
    Commercial Relationships  M.I. Klisovic, None; D.D. Klisovic, None; S.E. Katz, None; D. Effron, None; G. Marcucci, None.
  • Footnotes
    Support  Ohio Lions Research Association
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 1563. doi:
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      M.I. Klisovic, D.D. Klisovic, S.E. Katz, D. Effron, G. Marcucci; Depsipeptide (DP), Histone Deacetylase Inhibitor (HDACI), Inhibits Migration of Primary and Metastatic Uveal Melanoma (UM) Cells by Down-regulation of Matrix Metalloproteinase (MMP) 2 and 9 Gene Expression . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1563.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: UM is a malignant primary intraocular tumor in adults that has a high mortality rate due to hematogenous dissemination preferentially to the liver. The migration of UM cells through the basement membrane requires the presence of proteolytic enzymes such as MMPs. The expression of MMP-2 and MMP-9 in UM cells is a known risk factor for metastatic disease. We tested the ability of DP to inhibit UM cell migration in vitro and to down-regulate gene expression for MMP-2 and MMP-9. Methods: 3 primary and 2 metastatic (liver metastasis) UM cell lines were treated with DP (0,1,5 and 10 nM) for 24 hours. Migration of UM cells was studied in modified Boyden migration chambers for 24 hours (Hendrix et al. 1998) and only viable cells on both sides of the membrane were counted. Changes in MMP-2 and MMP-9 gene expression were studied by RT-PCR and confirmed with Western-blot. Levels of MMP-2 and MMP-9 in cell lysates were also quantified by ELISA assay. Results:Dose-dependent decrease in the migration of viable UM cells for primary and metastatic cell lines was observed (30-50 % inhibition). RT-PCR revealed dose-dependent down-regulation of gene expressions for MMP-2 and MMP-9 in all cell lines. This was confirmed by Western-blotting. ELISA assay revealed ~20-30% decrease in MMP-2 and MMP-9 protein content. Conclusions:DP inhibits primary and metastatic UM cell migration in vitro. Our data suggest that this inhibition of cell migration is mediated via down-regulation of MMP-2 and MMP-9 gene expression. DP may be a valuable adjunctive treatment modality for primary and metastatic UM in humans.

Keywords: melanoma • uvea • gene/expression 
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