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

Berta, Judit ; Török, Szilvia ; Tárnoki-Zách, Júlia ; Drozdovszky, Orsolya ; Tóvári, József ; Paku, Sándor ; Kovács, Ildikó ; Czirók, András ; Masri, Bernard and Megyesfalvi, Zsolt , et al. (2021) In Scientific Reports 11(1).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
11
issue
1
article number
5798
publisher
Nature Publishing Group
external identifiers
  • scopus:85102358230
  • pmid:33707612
ISSN
2045-2322
DOI
10.1038/s41598-021-85162-0
language
English
LU publication?
yes
id
34670b99-ee51-47ad-90a5-44d3c335542f
date added to LUP
2021-03-23 08:35:30
date last changed
2024-06-14 12:01:38
@article{34670b99-ee51-47ad-90a5-44d3c335542f,
  abstract     = {{<p>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.</p>}},
  author       = {{Berta, Judit and Török, Szilvia and Tárnoki-Zách, Júlia and Drozdovszky, Orsolya and Tóvári, József and Paku, Sándor and Kovács, Ildikó and Czirók, András and Masri, Bernard and Megyesfalvi, Zsolt and Oskolás, Henriett and Malm, Johan and Ingvar, Christian and Markó-Varga, György and Döme, Balázs and László, Viktória}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Apelin promotes blood and lymph vessel formation and the growth of melanoma lung metastasis}},
  url          = {{http://dx.doi.org/10.1038/s41598-021-85162-0}},
  doi          = {{10.1038/s41598-021-85162-0}},
  volume       = {{11}},
  year         = {{2021}},
}