The effects of modulation of MMP-2 and MMP-9 in angiogenesis and invasive pot...

科研人人

题名	The effects of modulation of MMP-2 and MMP-9 in angiogenesis and invasive potential in retinoblastoma
作者	Webb A.H., Saleh N., Gao B.T., Lee R.P., Lendermon J.B., Wilson M.W., Morales V.M.
杂志	Investigative Ophthalmology and Visual Science
年|卷|期	2015 56:7 (67)
链接	https://www-embase-com.consultaremota.upb.edu.co/search/results?subaction=viewrecord&rid=19&page=2&id=L615916495

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ARVO Annual Meeting Abstract  |   June 2015
The Effects of Modulation of MMP-2 and MMP-9 in Angiogenesis and Invasive Potential in Retinoblastoma
Anderson Hudgens Webb; Nabil Saleh; Bradley T Gao; Ryan P Lee; Justin B Lendermon; Matthew W Wilson; Vanessa Marie Morales

Investigative Ophthalmology & Visual Science June 2015, Vol.56, 67. doi:

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.