title: 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.affiliation: Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Coleman
authors.forename: Danielle
authors.initials: D
authors.lastname: Levine
authors.forename: Raj
authors.initials: R
authors.lastname: Kishore
authors.forename: Gangjian
authors.initials: G
authors.lastname: Qin
authors.forename: Tina
authors.initials: T
authors.lastname: Thorne
authors.forename: Erin
authors.initials: E
authors.lastname: Lambers
authors.forename: Sharath P
authors.initials: SP
authors.lastname: Sasi
authors.forename: Mina
authors.initials: M
authors.lastname: Yaar
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Gilchrest
authors.forename: David A
authors.initials: DA
authors.lastname: Goukassian