Inhibition of Melanoma Angiogenesis by Telomere Homolog Oligonucleotides

الملخص EN

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-1α.

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.