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Inhibition of Melanoma Angiogenesis by Telomere Homolog Oligonucleotides

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...

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Autores principales: Coleman, Christina, Levine, Danielle, Kishore, Raj, Qin, Gangjian, Thorne, Tina, Lambers, Erin, Sasi, Sharath P., Yaar, Mina, Gilchrest, Barbara A., Goukassian, David A.
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906154/
https://www.ncbi.nlm.nih.gov/pubmed/20652008
http://dx.doi.org/10.1155/2010/928628
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author Coleman, Christina
Levine, Danielle
Kishore, Raj
Qin, Gangjian
Thorne, Tina
Lambers, Erin
Sasi, Sharath P.
Yaar, Mina
Gilchrest, Barbara A.
Goukassian, David A.
author_facet Coleman, Christina
Levine, Danielle
Kishore, Raj
Qin, Gangjian
Thorne, Tina
Lambers, Erin
Sasi, Sharath P.
Yaar, Mina
Gilchrest, Barbara A.
Goukassian, David A.
author_sort Coleman, Christina
collection PubMed
description 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.
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spelling pubmed-29061542010-07-22 Inhibition of Melanoma Angiogenesis by Telomere Homolog Oligonucleotides Coleman, Christina Levine, Danielle Kishore, Raj Qin, Gangjian Thorne, Tina Lambers, Erin Sasi, Sharath P. Yaar, Mina Gilchrest, Barbara A. Goukassian, David A. J Oncol Research Article 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. Hindawi Publishing Corporation 2010 2010-06-28 /pmc/articles/PMC2906154/ /pubmed/20652008 http://dx.doi.org/10.1155/2010/928628 Text en Copyright © 2010 Christina Coleman et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Coleman, Christina
Levine, Danielle
Kishore, Raj
Qin, Gangjian
Thorne, Tina
Lambers, Erin
Sasi, Sharath P.
Yaar, Mina
Gilchrest, Barbara A.
Goukassian, David A.
Inhibition of Melanoma Angiogenesis by Telomere Homolog Oligonucleotides
title Inhibition of Melanoma Angiogenesis by Telomere Homolog Oligonucleotides
title_full Inhibition of Melanoma Angiogenesis by Telomere Homolog Oligonucleotides
title_fullStr Inhibition of Melanoma Angiogenesis by Telomere Homolog Oligonucleotides
title_full_unstemmed Inhibition of Melanoma Angiogenesis by Telomere Homolog Oligonucleotides
title_short Inhibition of Melanoma Angiogenesis by Telomere Homolog Oligonucleotides
title_sort inhibition of melanoma angiogenesis by telomere homolog oligonucleotides
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906154/
https://www.ncbi.nlm.nih.gov/pubmed/20652008
http://dx.doi.org/10.1155/2010/928628
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