June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
The Effects of Modulation of MMP-2 and MMP-9 in Angiogenesis and Invasive Potential in Retinoblastoma
Author Affiliations & Notes
  • Anderson Hudgens Webb
    Ophthalmology, University of Tennessee Health Science Center, Memphis, TN
  • Nabil Saleh
    Ophthalmology, University of Tennessee Health Science Center, Memphis, TN
  • Bradley T Gao
    Ophthalmology, University of Tennessee Health Science Center, Memphis, TN
  • Ryan P Lee
    Ophthalmology, University of Tennessee Health Science Center, Memphis, TN
  • Justin B Lendermon
    Ophthalmology, University of Tennessee Health Science Center, Memphis, TN
  • Matthew W Wilson
    Ophthalmology, University of Tennessee Health Science Center, Memphis, TN
  • Vanessa Marie Morales
    Ophthalmology, University of Tennessee Health Science Center, Memphis, TN
    Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN
  • Footnotes
    Commercial Relationships Anderson Webb, None; Nabil Saleh, None; Bradley Gao, None; Ryan Lee, None; Justin Lendermon, None; Matthew Wilson, None; Vanessa Morales, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 67. doi:
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    • Get Citation

      Anderson Hudgens Webb, Nabil Saleh, Bradley T Gao, Ryan P Lee, Justin B Lendermon, Matthew W Wilson, Vanessa Marie Morales; The Effects of Modulation of MMP-2 and MMP-9 in Angiogenesis and Invasive Potential in Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):67.

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

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Abstract

Purpose: Retinoblastoma (Rb) is the most common primary intraocular tumor in children. Effective local treatment exists, but occasionally Rb can metastasize. Metastases are attributed to extra-retina invasion of the ocular coats and the optic nerve. In this study we investigate modulation of Matrix Metalloproteinases (MMP), responsible for degradation of the extracellular matrix and invasion, as a potential adjuvant therapeutic target for Rb.

Methods: Three different Rb cell lines, Rb-Y79, Rb-Weri and Rb-355, were analyzed by gene expression, protein levels, and secretion of MMP-2 and MMP-9 by RT-PCR, Zymmography, and ELISA. Flow cytometry examined the levels of ICAM, VEGF, and CD31 as surrogates of adhesion, invasion, and angiogenesis. We evaluated the effect of pharmacological inhibition of MMP-2 (ARP100, Santa Cruz Biotechnology, Dallas, TX) and MMP-9 (AG-L-66085, Santa Cruz Biotechnology) by magnetic levitation (Nano3D Biosciences, Inc, Houston, TX) to determine their effects on angiogenesis and invasion.

Results: Our results show the three different Rb cell lines express different levels of MMP-2 and MMP-9 mRNA. MMP-9 expression increased upon cell activation by using Phorbol 12-myristate 13-acetate (PMA) and was reduced upon use of the MMP-2 and -9 inhibitors. Magnetic levitation analysis showed reduction in Rb tumor masses in vitro by pharmacological inhibition of MMP-2 and MMP-9.

Conclusions: Inhibition of MMP-2 and MMP-9, both markers of invasion, decreased expression of CD31 and VEGF, both markers of angiogenesis. MMP2 and MMP9 are potential candidates for targeted therapy.

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