Angiopoietin-2 inhibition using siRNA or the peptide antagonist L1–10 results in antitumor activity in human neuroblastoma

Saritha Sandra D'Souza and Scherzinger-Laude, Karine and Simon, Marc and Bharathi P. Salimath and Rössler, Jochen (2012) Angiopoietin-2 inhibition using siRNA or the peptide antagonist L1–10 results in antitumor activity in human neuroblastoma. Journal of Cancer Research and Clinical Oncology, 138 (12). pp. 2017-2026. ISSN 1432-1335

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Abstract

Purpose: The angiopoietin/Tie-2 system has been identified as a key role player in tumor angiogenesis. We investigated whether angiopoietin-2 could be a promising target in human neuroblastoma. Methods: Angiopoietin-2 down-regulation by siRNA or shRNA was evaluated in vitro in Kelly cells. Angiopoietin-2 shRNA-transfected Kelly cells were tested in a chorioallantoic membrane (CAM) assay to evaluate tumor growth and microvessel density. The effects of L1–10, a peptide–Fc fusion molecule blocking angiopoietin-2/Tie-2 interaction, administered 3 times/week were assessed in a murine neuroblastoma xenograft model. Results: Angiopoietin-2 down-regulation by siRNA or shRNA in Kelly cells inhibited cell proliferation and migration. In vivo growth and microvessel density of angiopoietin-2 shRNA-transfected Kelly cells in the CAM assay were reduced. Therapy of advanced tumors with L1–10 did not stop tumor progression. However, starting L1–10 treatment at the same time as neuroblastoma cell injection significantly inhibited tumor growth (vehicule: 903 ± 160 mm3; L1–10: 270 ± 152 mm3 after 26 days; P < 0.05). Microvessel density was reduced in both L1–10-treated tumors, whereas expression of angiopoietin-2 and VEGF-A did not change. Conclusion: This first demonstration of beneficial angiopoietin-2 inhibition in neuroblastoma offers an additional approach for future therapy strategies, especially by using L1–10 in the setting of minimal residual disease.

Item Type:	Article
Uncontrolled Keywords:	Angiopoietin-2 Tie-2 L1–10 siRNA Microvessel density Childhood neuroblastoma
Subjects:	B Life Science > Biotechnology
Divisions:	Department of > Biotechnology
Depositing User:	C Swapna Library Assistant
Date Deposited:	12 Jul 2019 06:14
Last Modified:	09 May 2023 07:52
URI:	http://eprints.uni-mysore.ac.in/id/eprint/5129

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