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.
