Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
Organisations
External organisations
  • National Korányi Institute for Tuberculosis and Pulmonology, Hungary
  • Eötvös Loránd University
  • National Institute of Oncology, Budapest
  • Semmelweis University
  • University of Kansas Cancer Center
  • Institut Cochin
  • Medical University of Vienna
  • Skåne University Hospital
  • University of Kansas
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Article number5798
JournalScientific Reports
Volume11
Issue number1
Publication statusPublished - 2021
Publication categoryResearch
Peer-reviewedYes