Sequential Loss of Tumor Vessel Pericytes and Endothelial Cells after Inhibition of Platelet-Derived Growth Factor B by Selective Aptamer AX102

• DOI: 10.1158/0008-5472.can-07-0293
• Publication Date: 2007-08-01T18:34:13Z
• Authors: Barbara Sennino; Beverly L. Falcón; Dilara McCauley; Tom Le; Thomas McCauley; Jeffrey C. Kurz; Amy Haskell; David M. Epstein; Donald M. McDonald
• Keywords: Pericyte; Vascularity; Platelet-derived growth factor; Vascular permeability

Abstract Inhibition of platelet derived growth factor (PDGF) can increase the efficacy other cancer therapeutics, but cellular mechanism is incompletely understood. We examined effects on tumor vasculature a novel DNA oligonucleotide aptamer (AX102) that selectively binds PDGF-B. Treatment with AX102 led to progressive reduction pericytes, identified by PDGF receptor β, NG2, desmin, or α-smooth muscle actin immunoreactivity, in Lewis lung carcinomas. The decrease ranged from 35% at 2 days, 63% 7 85% 28 days. Most vessels lacked pericytes days subsequently regressed. Overall vascularity decreased 79% over without corresponding size. Regression and endothelial cells empty basement membrane sleeves, which were visible only 54% remained PDGF-B inhibition had less pronounced effect pancreatic islet tumors RIP-Tag2 transgenic mice, where 47%, 38%, sleeves 21% Taken together, these findings show signaling lead regression vessels, magnitude specific does not necessarily retard growth. Loss an expected direct consequence blockade, reduced likely be secondary pericyte regression. [Cancer Res 2007;67(15):7358–67]