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Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy

Antiangiogenic agents transiently normalize tumor vessel structure and improve vessel function, thereby providing a window of opportunity for enhancing the efficacy of chemotherapy or radiotherapy. Currently, there are no reliable predictors or markers reflecting this vessel normalization window dur...

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Detalles Bibliográficos
Autores principales: Zhang, Li, Takara, Kazuhiro, Yamakawa, Daishi, Kidoya, Hiroyasu, Takakura, Nobuyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724822/
https://www.ncbi.nlm.nih.gov/pubmed/26475217
http://dx.doi.org/10.1111/cas.12836
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author Zhang, Li
Takara, Kazuhiro
Yamakawa, Daishi
Kidoya, Hiroyasu
Takakura, Nobuyuki
author_facet Zhang, Li
Takara, Kazuhiro
Yamakawa, Daishi
Kidoya, Hiroyasu
Takakura, Nobuyuki
author_sort Zhang, Li
collection PubMed
description Antiangiogenic agents transiently normalize tumor vessel structure and improve vessel function, thereby providing a window of opportunity for enhancing the efficacy of chemotherapy or radiotherapy. Currently, there are no reliable predictors or markers reflecting this vessel normalization window during antiangiogenic therapy. Apelin, the expression of which is regulated by hypoxia, and which has well‐described roles in tumor progression, is an easily measured secreted protein. Here, we show that apelin can be used as a marker for the vessel normalization window during antiangiogenic therapy. Mice bearing s.c. tumors resulting from inoculation of the colon adenocarcinoma cell line HT29 were treated with a single injection of bevacizumab, a mAb neutralizing vascular endothelial growth factor. Tumor growth, vessel density, pericyte coverage, tumor hypoxia, and small molecule delivery were determined at four different times after treatment with bevacizumab (days 1, 3, 5, and 8). Tumor growth and vessel density were significantly reduced after bevacizumab treatment, which also significantly increased tumor vessel maturity, and improved tumor hypoxia and small molecule delivery between days 3 and 5. These effects abated by day 8, suggesting that a time window for vessel normalization was opened between days 3 and 5 during bevacizumab treatment in this model. Apelin mRNA expression and plasma apelin levels decreased transiently at day 5 post‐treatment, coinciding with vessel normalization. Thus, apelin is a potential indicator of the vessel normalization window during antiangiogenic therapy.
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spelling pubmed-47248222016-02-03 Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy Zhang, Li Takara, Kazuhiro Yamakawa, Daishi Kidoya, Hiroyasu Takakura, Nobuyuki Cancer Sci Original Articles Antiangiogenic agents transiently normalize tumor vessel structure and improve vessel function, thereby providing a window of opportunity for enhancing the efficacy of chemotherapy or radiotherapy. Currently, there are no reliable predictors or markers reflecting this vessel normalization window during antiangiogenic therapy. Apelin, the expression of which is regulated by hypoxia, and which has well‐described roles in tumor progression, is an easily measured secreted protein. Here, we show that apelin can be used as a marker for the vessel normalization window during antiangiogenic therapy. Mice bearing s.c. tumors resulting from inoculation of the colon adenocarcinoma cell line HT29 were treated with a single injection of bevacizumab, a mAb neutralizing vascular endothelial growth factor. Tumor growth, vessel density, pericyte coverage, tumor hypoxia, and small molecule delivery were determined at four different times after treatment with bevacizumab (days 1, 3, 5, and 8). Tumor growth and vessel density were significantly reduced after bevacizumab treatment, which also significantly increased tumor vessel maturity, and improved tumor hypoxia and small molecule delivery between days 3 and 5. These effects abated by day 8, suggesting that a time window for vessel normalization was opened between days 3 and 5 during bevacizumab treatment in this model. Apelin mRNA expression and plasma apelin levels decreased transiently at day 5 post‐treatment, coinciding with vessel normalization. Thus, apelin is a potential indicator of the vessel normalization window during antiangiogenic therapy. John Wiley and Sons Inc. 2015-11-12 2016-01 /pmc/articles/PMC4724822/ /pubmed/26475217 http://dx.doi.org/10.1111/cas.12836 Text en © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Zhang, Li
Takara, Kazuhiro
Yamakawa, Daishi
Kidoya, Hiroyasu
Takakura, Nobuyuki
Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy
title Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy
title_full Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy
title_fullStr Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy
title_full_unstemmed Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy
title_short Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy
title_sort apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724822/
https://www.ncbi.nlm.nih.gov/pubmed/26475217
http://dx.doi.org/10.1111/cas.12836
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