Apelin inhibition prevents resistance and metastasis associated with anti-angiogenic therapy.
EMBO Mol Med
; 11(8): e9266, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-31267692
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Movimento Celular
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Resistencia a Medicamentos Antineoplásicos
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Inibidores da Angiogênese
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Inibidores de Proteínas Quinases
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Apelina
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Receptores de Apelina
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Sunitinibe
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Neoplasias Pulmonares
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Neoplasias Mamárias Experimentais
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Neovascularização Patológica
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article