Novel anti IGFBP2 single chain variable fragment inhibits glioma cell migration and invasion

Patil, Shilpa S and Railkar, Reema and Swain, Monalisa and Atreya, Hanudatta S and Dighe, Rajan R and Kondaiah, Paturu (2015) Novel anti IGFBP2 single chain variable fragment inhibits glioma cell migration and invasion. In: JOURNAL OF NEURO-ONCOLOGY, 123 (2). pp. 225-235.

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Abstract

Insulin like growth factor binding protein 2 (IGFBP2) is highly up regulated in glioblastoma (GBM) tissues and has been one of the prognostic indicators. There are compelling evidences suggesting important roles for IGFBP2 in glioma cell proliferation, migration and invasion. Extracellular IGFBP2 through its carboxy terminal arginine glycine aspartate (RGD) motif can bind to cell surface alpha 5 beta 1 integrins and activate pathways downstream to integrin signaling. This IGFBP2 activated integrin signaling is known to play a crucial role in IGFBP2 mediated invasion of glioma cells. Hence a molecular inhibitor of carboxy terminal domain of IGFBP2 which can inhibit IGFBP2-cell surface interaction is of great therapeutic importance. In an attempt to develop molecular inhibitors of IGFBP2, we screened single chain variable fragment (scFv) phage display libraries, Tomlinson I (Library size 1.47 x 10(8)) and Tomlinson J (Library size 1.37 x 10(8)) using human recombinant IGFBP2. After screening we obtained three IGFBP2 specific binders out of which one scFv B7J showed better binding to IGFBP2 at its carboxy terminal domain, blocked IGFBP2-cell surface association, reduced activity of matrix metalloprotease 2 in the conditioned medium of glioma cells and inhibited IGFBP2 induced migration and invasion of glioma cells. We demonstrate for the first time that in vitro inhibition of extracellular IGFBP2 activity by using human scFv results in significant reduction of glioma cell migration and invasion. Therefore, the inhibition of IGFBP2 can serve as a potential therapeutic strategy in the management of GBM.

Item Type:	Journal Article
Publication:	JOURNAL OF NEURO-ONCOLOGY
Publisher:	SPRINGER
Additional Information:	Copy right for this article belongs to the SPRINGER, 233 SPRING ST, NEW YORK, NY 10013 USA
Keywords:	IGFBP2; scFv; Glioma; Invasion
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics Division of Chemical Sciences > NMR Research Centre (Formerly Sophisticated Instruments Facility)
Date Deposited:	19 Jul 2015 06:16
Last Modified:	19 Jul 2015 06:16
URI:	http://eprints.iisc.ac.in/id/eprint/51819

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