Inhibition of melanoma angiogenesis by telomere homolog oligonucleotides

David A. Goukassian, Christina Coleman, Danielle Levine, Raj Kishore, Gangjian Qin, Tina Thorne, Erin Lambers, Sharath P. Sasi, Mina Yaar, Barbara A. Gilchrest

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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-1 . 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.

Original languageEnglish (US)
Article number928628
JournalJournal of Oncology
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Oncology

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