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Inhibition of In Vivo Tumor Angiogenesis and Growth Via Systemic Delivery of an Angiopoietin 2-Specific RNA Aptamer
- Source :
-
Journal of Surgical Research . May2008, Vol. 146 Issue 1, p16-23. 8p. - Publication Year :
- 2008
-
Abstract
- Background: Cellular events mediated by the Tie2 receptor are important to tumor neovascularization. Despite the complex interplay of the best-characterized Tie2 ligands, angiopoietins 1 and 2, Ang2 is purportedly “proangiogenic” in the presence of vascular endothelial growth factor. We examined whether in vivo administration of an RNA aptamer that specifically blocks Ang 2 would inhibit tumor angiogenesis and growth. Methods: Ang2-mediated Tie2 receptor phosphorylation was assessed in vitro in the absence and presence of aptamer coupled to polyethylene glycol. In vivo angiogenesis assay: CT26 murine colon carcinoma cells expressing green fluorescent protein were delivered into mouse dorsal skinfold window chambers. Animals received daily intraperitoneal injections of phosphate-buffered saline, low-dose (Ang2 aptamer-LD; 1 mg/kg/d), or high-dose aptamer (Ang2 aptamer-HD; 10 mg/kg/d). Vascular length density was measured under fluorescence microscopy. Primary tumor growth: CT26 cells expressing luciferase were injected into flanks of BALB/c mice to allow tumor growth monitoring by bioluminescence imaging. Animals received continuous phosphate-buffered saline or aptamer (1 mg/kg/d) via ALZET pumps. Tumors were assessed for CD31/PECAM-1 immunostaining and Hoechst dye uptake. Results: Pegylated aptamer inhibited Tie2 phosphorylation. Systemic aptamer administration reduced vascular length density (P ≤ 0.03) and decreased bioluminescence emission (P < 0.04), corresponding to 50% decrease in tumor volume (P = 0.04). Control tumors displayed abundant vascular marker staining, in contrast to tumors from aptamer-treated animals. Conclusions: in vivo administration of a clinically relevant, pegylated RNA aptamer specifically designed against Ang2 inhibited tumor angiogenesis and growth. These findings support targeted Ang2 inhibition as a relevant anti-angiogenic, anti-neoplastic strategy. [Copyright &y& Elsevier]
- Subjects :
- *TUMORS
*PATHOLOGY
*CYSTS (Pathology)
*GREEN fluorescent protein
Subjects
Details
- Language :
- English
- ISSN :
- 00224804
- Volume :
- 146
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Surgical Research
- Publication Type :
- Academic Journal
- Accession number :
- 31564692
- Full Text :
- https://doi.org/10.1016/j.jss.2007.04.028