Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis.
Animals
Apelin
/ adverse effects
Case-Control Studies
Cell Line, Tumor
Cell Movement
Cell Proliferation
Female
Humans
Lung Neoplasms
/ blood
Lymphangiogenesis
Male
Melanoma, Experimental
/ blood
Mice
Middle Aged
Neoplasm Invasiveness
Neovascularization, Pathologic
/ blood
Vascular Endothelial Growth Factor A
/ blood
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
11 03 2021
11 03 2021
Historique:
received:
28
09
2020
accepted:
24
02
2021
entrez:
12
3
2021
pubmed:
13
3
2021
medline:
15
12
2021
Statut:
epublish
Résumé
Apelin, a ligand of the APJ receptor, is overexpressed in several human cancers and plays an important role in tumor angiogenesis and growth in various experimental systems. We investigated the role of apelin signaling in the malignant behavior of cutaneous melanoma. Murine B16 and human A375 melanoma cell lines were stably transfected with apelin encoding or control vectors. Apelin overexpression significantly increased melanoma cell migration and invasion in vitro, but it had no impact on its proliferation. In our in vivo experiments, apelin significantly increased the number and size of lung metastases of murine melanoma cells. Melanoma cell proliferation rates and lymph and blood microvessel densities were significantly higher in the apelin-overexpressing pulmonary metastases. APJ inhibition by the competitive APJ antagonist MM54 significantly attenuated the in vivo pro-tumorigenic effects of apelin. Additionally, we detected significantly elevated circulating apelin and VEGF levels in patients with melanoma compared to healthy controls. Our results show that apelin promotes blood and lymphatic vascularization and the growth of pulmonary metastases of skin melanoma. Further studies are warranted to validate apelin signaling as a new potential therapeutic target in this malignancy.
Identifiants
pubmed: 33707612
doi: 10.1038/s41598-021-85162-0
pii: 10.1038/s41598-021-85162-0
pmc: PMC7952702
doi:
Substances chimiques
Apelin
0
Vascular Endothelial Growth Factor A
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5798Références
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