Inhibition of melanoma angiogenesis by telomere homolog oligonucleotides.

Abstract

Telomere homolog oligonucleotides (T-oligos) activate an innate telomere-based program that leads to multiple anticancer effects. T-oligos act at telomeres to initiate signaling through the Werner protein and ATM kinase. We wanted to determine if T-oligos have antiangiogenic effects. We found that T-oligo-treated human melanoma (MM-AN) cells had decreased expression of vascular endothelial growth factor (VEGF), VEGF receptor 2, angiopoeitin-1 and -2 and decreased VEGF secretion. T-oligos activated the transcription factor E2F1 and inhibited the activity of the angiogenic transcription factor, HIF-1alpha. T-oligos inhibited EC tubulogenesis and total tumor microvascular density matrix invasion by MM-AN cells and ECs in vitro. In melanoma SCID xenografts, two systemic T-oligo injections decreased by 60% (P < .004) total tumor microvascular density and the functional vessels density by 80% (P < .002). These findings suggest that restriction of tumor angiogenesis is among the host's innate telomere-based anticancer responses and provide further evidence that T-oligos may offer a powerful new approach for melanoma treatment.

• Authors: Christina Coleman, Danielle Levine, Raj Kishore, Gangjian Qin, Tina Thorne, Erin Lambers, Sharath P Sasi, Mina Yaar, Barbara A Gilchrest, David A Goukassian
• Journal: Journal of oncology (J Oncol) Vol. 2010 Pg. 928628 ( 2010) ISSN: 1687-8469 [Electronic] Egypt
• PMID: 20652008 (Publication Type: Journal Article)