Apelin promotes lymphangiogenesis and lymph node metastasis

Judit Berta, Mir Alireza Hoda, Viktoria Laszlo, Anita Rozsas, Tamas Garay, Szilvia Torok, Michael Grusch, Walter Berger, Sandor Paku, Ferenc Renyi-Vamos, Bernard Masri, Jozsef Tovari, Marion Groger, Walter Klepetko, Balazs Hegedus, Balazs Dome

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Whereas the role of the G-protein-coupled APJ receptor and its ligand, apelin, in angiogenesis has been well documented, the ability of the apelin/APJ system to induce lymphangiogenesis and lymphatic metastasis has been largely unexplored. To this end, we first show that APJ is expressed in lymphatic endothelial cells (LECs) and, moreover, that it responds to apelin by activating the apelinergic signaling cascade. We find that although apelin treatment does not influence the proliferation of LECs in vitro, it enhances their migration, protects them against UV irradiation-induced apoptosis, increases their spheroid numbers in 3D culture, stimulates their in vitro capillary-like tube formation and, furthermore, promotes the invasive growth of lymphatic microvessels in vivo in the matrigel plug assay. We also demonstrate that apelin overexpression in malignant cells is associated with accelerated in vivo tumor growth and with increased intratumoral lymphangiogenesis and lymph node metastasis. These results indicate that apelin induces lymphangiogenesis and, accordingly, plays an important role in lymphatic tumor progression. Our study does not only reveal apelin as a novel lymphangiogenic factor but might also open the door for the development of novel anticancer therapies targeting lymphangiogenesis.

Original languageEnglish
Pages (from-to)4426-4437
Number of pages12
JournalOncotarget
Volume5
Issue number12
DOIs
Publication statusPublished - 2014

Keywords

  • APJ
  • Apelin
  • Lymph node metastasis
  • Lymphangiogenesis

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Berta, J., Hoda, M. A., Laszlo, V., Rozsas, A., Garay, T., Torok, S., Grusch, M., Berger, W., Paku, S., Renyi-Vamos, F., Masri, B., Tovari, J., Groger, M., Klepetko, W., Hegedus, B., & Dome, B. (2014). Apelin promotes lymphangiogenesis and lymph node metastasis. Oncotarget, 5(12), 4426-4437. https://doi.org/10.18632/oncotarget.2032