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Inhibition of in vivo tumor angiogenesis and growth via systemic delivery of an angiopoietin 2-specific RNA aptamer.

Publication ,  Journal Article
Sarraf-Yazdi, S; Mi, J; Moeller, BJ; Niu, X; White, RR; Kontos, CD; Sullenger, BA; Dewhirst, MW; Clary, BM
Published in: J Surg Res
May 1, 2008

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 < or = 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.

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Published In

J Surg Res

DOI

ISSN

0022-4804

Publication Date

May 1, 2008

Volume

146

Issue

1

Start / End Page

16 / 23

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Surgery
  • Receptor, TIE-2
  • Phosphorylation
  • Neovascularization, Pathologic
  • Mice, Inbred BALB C
  • Mice
  • Female
  • Dose-Response Relationship, Drug
  • Colonic Neoplasms
 

Citation

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Sarraf-Yazdi, S., Mi, J., Moeller, B. J., Niu, X., White, R. R., Kontos, C. D., … Clary, B. M. (2008). Inhibition of in vivo tumor angiogenesis and growth via systemic delivery of an angiopoietin 2-specific RNA aptamer. J Surg Res, 146(1), 16–23. https://doi.org/10.1016/j.jss.2007.04.028
Sarraf-Yazdi, Shiva, Jing Mi, Benjamin J. Moeller, Xilin Niu, Rebekah R. White, Christopher D. Kontos, Bruce A. Sullenger, Mark W. Dewhirst, and Bryan M. Clary. “Inhibition of in vivo tumor angiogenesis and growth via systemic delivery of an angiopoietin 2-specific RNA aptamer.J Surg Res 146, no. 1 (May 1, 2008): 16–23. https://doi.org/10.1016/j.jss.2007.04.028.
Sarraf-Yazdi S, Mi J, Moeller BJ, Niu X, White RR, Kontos CD, et al. Inhibition of in vivo tumor angiogenesis and growth via systemic delivery of an angiopoietin 2-specific RNA aptamer. J Surg Res. 2008 May 1;146(1):16–23.
Sarraf-Yazdi, Shiva, et al. “Inhibition of in vivo tumor angiogenesis and growth via systemic delivery of an angiopoietin 2-specific RNA aptamer.J Surg Res, vol. 146, no. 1, May 2008, pp. 16–23. Pubmed, doi:10.1016/j.jss.2007.04.028.
Sarraf-Yazdi S, Mi J, Moeller BJ, Niu X, White RR, Kontos CD, Sullenger BA, Dewhirst MW, Clary BM. Inhibition of in vivo tumor angiogenesis and growth via systemic delivery of an angiopoietin 2-specific RNA aptamer. J Surg Res. 2008 May 1;146(1):16–23.
Journal cover image

Published In

J Surg Res

DOI

ISSN

0022-4804

Publication Date

May 1, 2008

Volume

146

Issue

1

Start / End Page

16 / 23

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Surgery
  • Receptor, TIE-2
  • Phosphorylation
  • Neovascularization, Pathologic
  • Mice, Inbred BALB C
  • Mice
  • Female
  • Dose-Response Relationship, Drug
  • Colonic Neoplasms