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Different angioregulatory activity of monovalent galectin-9 isoforms

Aanhane, Ed; Schulkens, Iris A.; Heusschen, Roy; Castricum, Kitty; Leffler, Hakon LU ; Griffioen, Arjan W. and Thijssen, Victor L. (2018) In Angiogenesis p.1-11
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
in press
subject
keywords
Angiogenesis, Blood vessels, Cancer, Galectin, Sprouting, Tube formation
in
Angiogenesis
pages
11 pages
publisher
Springer Netherlands
external identifiers
  • scopus:85045069906
ISSN
0969-6970
DOI
10.1007/s10456-018-9607-8
language
English
LU publication?
yes
id
7768c603-0dd7-4278-b9d7-20b9e7fda5b2
date added to LUP
2018-04-20 14:24:53
date last changed
2018-08-19 04:42:23
@article{7768c603-0dd7-4278-b9d7-20b9e7fda5b2,
  abstract     = {<p>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.</p>},
  author       = {Aanhane, Ed and Schulkens, Iris A. and Heusschen, Roy and Castricum, Kitty and Leffler, Hakon and Griffioen, Arjan W. and Thijssen, Victor L.},
  issn         = {0969-6970},
  keyword      = {Angiogenesis,Blood vessels,Cancer,Galectin,Sprouting,Tube formation},
  language     = {eng},
  month        = {03},
  pages        = {1--11},
  publisher    = {Springer Netherlands},
  series       = {Angiogenesis},
  title        = {Different angioregulatory activity of monovalent galectin-9 isoforms},
  url          = {http://dx.doi.org/10.1007/s10456-018-9607-8},
  year         = {2018},
}