| First Author | Uribesalgo I | Year | 2019 |
| Journal | EMBO Mol Med | Volume | 11 |
| Issue | 8 | Pages | e9266 |
| PubMed ID | 31267692 | Mgi Jnum | J:290544 |
| Mgi Id | MGI:6443903 | Doi | 10.15252/emmm.201809266 |
| Citation | Uribesalgo I, et al. (2019) Apelin inhibition prevents resistance and metastasis associated with anti-angiogenic therapy. EMBO Mol Med 11(8):e9266 |
| abstractText | 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. |
