Apelin inhibition prevents resistance and metastasis associated with anti‐angiogenic therapy
Abstract: 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.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Apelin inhibition prevents resistance and metastasis associated with anti‐angiogenic therapy ; volume:11 ; number:8 ; year:2019 ; extent:19
EMBO molecular medicine / European Molecular Biology Organization ; 11, Heft 8 (2019) (gesamt 19)
- Urheber
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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 Martin
- DOI
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10.15252/emmm.201809266
- URN
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urn:nbn:de:101:1-2022080307094273452437
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:33 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- 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 Martin
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