Different angioregulatory activity of monovalent galectin-9 isoforms

Research output: Contribution to journalArticle

Abstract

Galectin-9 consists of two peptide-linked carbohydrate recognition domains (CRDs), but alternative splicing and proteolytic processing can give rise to multiple galectin-9 isoforms. Some of these consist of a single CRD and can exert different functions in cell biology. Here, we explored the role of these galectin-9 isoforms in endothelial cell function and angiogenesis. For this, we compared the effects of the two separate CRDs (Gal-9N and Gal-9C) with the tandem repeat galectin-9M on endothelial cell proliferation, migration, sprouting and tube formation in vitro as well as on angiogenesis in vivo using the chicken chorioallantoic membrane (CAM) assay. Galectin-9 isoforms significantly affected proliferation in quiescent endothelial cells and migration in activated endothelial cells. Interestingly, both monovalent gal-9 CRDs displayed opposite effects compared to gal-9M on proliferation and migration. Sprouting was significantly inhibited by gal-9C, while all isoforms appeared to stimulate tube formation. Angiogenesis in vivo was hampered by all three isoforms with predominant effects on vessel length. In general, the isoforms induced only subtle concentration-dependent effects in vitro as well as in vivo. Collectively, the effects of different galectin-9 isoforms in endothelial cell biology depend on the cellular activation status. While opposing effects can be observed on a cellular level in vitro, all galectin-9 isoforms hamper angiogenesis in vivo. This warrants further investigation of the regulatory mechanisms that underlie the diverging roles of galectin-9 isoforms in endothelial cell biology since this could provide therapeutic opportunities.

Details

Authors
  • Ed Aanhane
  • Iris A. Schulkens
  • Roy Heusschen
  • Kitty Castricum
  • Hakon Leffler
  • Arjan W. Griffioen
  • Victor L. Thijssen
Organisations
External organisations
  • Amsterdam UMC - Vrije Universiteit Amsterdam
  • University of Liège
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
  • Hematology

Keywords

  • Angiogenesis, Blood vessels, Cancer, Galectin, Sprouting, Tube formation
Original languageEnglish
Pages (from-to)545-555
JournalAngiogenesis
Volume21
Issue number3
Publication statusPublished - 2018 Aug
Publication categoryResearch
Peer-reviewedYes