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Inhibition of receptor signaling and of glioblastoma-derived tumor growth by a novel PDGFRß aptamer.

Authors: Camorani, Simona  Esposito, Carla L  Rienzo, Anna  Catuogno, Silvia  Iaboni, Margherita  Condorelli, Gerolama  de Franciscis, Vittorio  Cerchia, Laura 
Citation: Camorani S, etal., Mol Ther. 2014 Apr;22(4):828-41. doi: 10.1038/mt.2013.300. Epub 2014 Jan 2.
Pubmed: (View Article at PubMed) PMID:24566984
DOI: Full-text: DOI:10.1038/mt.2013.300

Platelet-derived growth factor receptor ß (PDGFRß) is a cell-surface tyrosine kinase receptor implicated in several cellular processes including proliferation, migration, and angiogenesis. It represents a compelling therapeutic target in many human tumors, including glioma. A number of tyrosine kinase inhibitors under development as antitumor agents have been found to inhibit PDGFRß. However, they are not selective as they present multiple tyrosine kinase targets. Here, we report a novel PDGFRß-specific antagonist represented by a nuclease-resistant RNA-aptamer, named Gint4.T. This aptamer is able to specifically bind to the human PDGFRß ectodomain (Kd: 9.6¿nmol/l) causing a strong inhibition of ligand-dependent receptor activation and of downstream signaling in cell lines and primary cultures of human glioblastoma cells. Moreover, Gint4.T aptamer drastically inhibits cell migration and proliferation, induces differentiation, and blocks tumor growth in vivo. In addition, Gint4.T aptamer prevents PDGFRß heterodimerization with and resultant transactivation of epidermal growth factor receptor. As a result, the combination of Gint4.T and an epidermal growth factor receptor-targeted aptamer is better at slowing tumor growth than either single aptamer alone. These findings reveal Gint4.T as a PDGFRß-drug candidate with translational potential.

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CRRD Object Information
CRRD ID: 13702903
Created: 2018-07-24
Species: All species
Last Modified: 2018-07-24
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.