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Apelin inhibition prevents resistance and metastasis associated with anti‐angiogenic therapy
Angiogenesis is a hallmark of cancer, promoting growth and metastasis. Anti‐angiogenic treatment has limited efficacy due to therapy‐induced blood vessel alterations, often followed by local hypoxia, tumor adaptation, progression, and metastasis. It is therefore paramount to overcome therapy‐induced...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685079/ https://www.ncbi.nlm.nih.gov/pubmed/31267692 http://dx.doi.org/10.15252/emmm.201809266 |
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author | Uribesalgo, Iris Hoffmann, David Zhang, Yin Kavirayani, Anoop Lazovic, Jelena Berta, Judit Novatchkova, Maria Pai, Tsung‐Pin Wimmer, Reiner A László, Viktória Schramek, Daniel Karim, Rezaul Tortola, Luigi Deswal, Sumit Haas, Lisa Zuber, Johannes Szűcs, Miklós Kuba, Keiji Dome, Balazs Cao, Yihai Haubner, Bernhard J Penninger, Josef M |
author_facet | Uribesalgo, Iris Hoffmann, David Zhang, Yin Kavirayani, Anoop Lazovic, Jelena Berta, Judit Novatchkova, Maria Pai, Tsung‐Pin Wimmer, Reiner A László, Viktória Schramek, Daniel Karim, Rezaul Tortola, Luigi Deswal, Sumit Haas, Lisa Zuber, Johannes Szűcs, Miklós Kuba, Keiji Dome, Balazs Cao, Yihai Haubner, Bernhard J Penninger, Josef M |
author_sort | Uribesalgo, Iris |
collection | PubMed |
description | Angiogenesis is a hallmark of cancer, promoting growth and metastasis. Anti‐angiogenic treatment has limited efficacy due to therapy‐induced blood vessel alterations, often followed by local hypoxia, tumor adaptation, progression, and metastasis. It is therefore paramount to overcome therapy‐induced resistance. We show that Apelin inhibition potently remodels the tumor microenvironment, reducing angiogenesis, and effectively blunting tumor growth. Functionally, targeting Apelin improves vessel function and reduces polymorphonuclear myeloid‐derived suppressor cell infiltration. Importantly, in mammary and lung cancer, Apelin prevents resistance to anti‐angiogenic receptor tyrosine kinase (RTK) inhibitor therapy, reducing growth and angiogenesis in lung and breast cancer models without increased hypoxia in the tumor microenvironment. Apelin blockage also prevents RTK inhibitor‐induced metastases, and high Apelin levels correlate with poor prognosis of anti‐angiogenic therapy patients. These data identify a druggable anti‐angiogenic drug target that reduces tumor blood vessel densities and normalizes the tumor vasculature to decrease metastases. |
format | Online Article Text |
id | pubmed-6685079 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66850792019-08-12 Apelin inhibition prevents resistance and metastasis associated with anti‐angiogenic therapy Uribesalgo, Iris Hoffmann, David Zhang, Yin Kavirayani, Anoop Lazovic, Jelena Berta, Judit Novatchkova, Maria Pai, Tsung‐Pin Wimmer, Reiner A László, Viktória Schramek, Daniel Karim, Rezaul Tortola, Luigi Deswal, Sumit Haas, Lisa Zuber, Johannes Szűcs, Miklós Kuba, Keiji Dome, Balazs Cao, Yihai Haubner, Bernhard J Penninger, Josef M EMBO Mol Med Articles Angiogenesis is a hallmark of cancer, promoting growth and metastasis. Anti‐angiogenic treatment has limited efficacy due to therapy‐induced blood vessel alterations, often followed by local hypoxia, tumor adaptation, progression, and metastasis. It is therefore paramount to overcome therapy‐induced resistance. We show that Apelin inhibition potently remodels the tumor microenvironment, reducing angiogenesis, and effectively blunting tumor growth. Functionally, targeting Apelin improves vessel function and reduces polymorphonuclear myeloid‐derived suppressor cell infiltration. Importantly, in mammary and lung cancer, Apelin prevents resistance to anti‐angiogenic receptor tyrosine kinase (RTK) inhibitor therapy, reducing growth and angiogenesis in lung and breast cancer models without increased hypoxia in the tumor microenvironment. Apelin blockage also prevents RTK inhibitor‐induced metastases, and high Apelin levels correlate with poor prognosis of anti‐angiogenic therapy patients. These data identify a druggable anti‐angiogenic drug target that reduces tumor blood vessel densities and normalizes the tumor vasculature to decrease metastases. John Wiley and Sons Inc. 2019-06-24 2019-08 /pmc/articles/PMC6685079/ /pubmed/31267692 http://dx.doi.org/10.15252/emmm.201809266 Text en © 2019 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Uribesalgo, Iris Hoffmann, David Zhang, Yin Kavirayani, Anoop Lazovic, Jelena Berta, Judit Novatchkova, Maria Pai, Tsung‐Pin Wimmer, Reiner A László, Viktória Schramek, Daniel Karim, Rezaul Tortola, Luigi Deswal, Sumit Haas, Lisa Zuber, Johannes Szűcs, Miklós Kuba, Keiji Dome, Balazs Cao, Yihai Haubner, Bernhard J Penninger, Josef M Apelin inhibition prevents resistance and metastasis associated with anti‐angiogenic therapy |
title | Apelin inhibition prevents resistance and metastasis associated with anti‐angiogenic therapy |
title_full | Apelin inhibition prevents resistance and metastasis associated with anti‐angiogenic therapy |
title_fullStr | Apelin inhibition prevents resistance and metastasis associated with anti‐angiogenic therapy |
title_full_unstemmed | Apelin inhibition prevents resistance and metastasis associated with anti‐angiogenic therapy |
title_short | Apelin inhibition prevents resistance and metastasis associated with anti‐angiogenic therapy |
title_sort | apelin inhibition prevents resistance and metastasis associated with anti‐angiogenic therapy |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685079/ https://www.ncbi.nlm.nih.gov/pubmed/31267692 http://dx.doi.org/10.15252/emmm.201809266 |
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