Different angioregulatory activity of monovalent galectin-9 isoforms

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Different angioregulatory activity of monovalent galectin-9 isoforms. / Aanhane, Ed; Schulkens, Iris A.; Heusschen, Roy; Castricum, Kitty; Leffler, Hakon; Griffioen, Arjan W.; Thijssen, Victor L.

I: Angiogenesis, Vol. 21, Nr. 3, 08.2018, s. 545-555.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Aanhane, E, Schulkens, IA, Heusschen, R, Castricum, K, Leffler, H, Griffioen, AW & Thijssen, VL 2018, 'Different angioregulatory activity of monovalent galectin-9 isoforms', Angiogenesis, vol. 21, nr. 3, s. 545-555. https://doi.org/10.1007/s10456-018-9607-8

APA

Aanhane, E., Schulkens, I. A., Heusschen, R., Castricum, K., Leffler, H., Griffioen, A. W., & Thijssen, V. L. (2018). Different angioregulatory activity of monovalent galectin-9 isoforms. Angiogenesis, 21(3), 545-555. https://doi.org/10.1007/s10456-018-9607-8

CBE

Aanhane E, Schulkens IA, Heusschen R, Castricum K, Leffler H, Griffioen AW, Thijssen VL. 2018. Different angioregulatory activity of monovalent galectin-9 isoforms. Angiogenesis. 21(3):545-555. https://doi.org/10.1007/s10456-018-9607-8

MLA

Vancouver

Aanhane E, Schulkens IA, Heusschen R, Castricum K, Leffler H, Griffioen AW et al. Different angioregulatory activity of monovalent galectin-9 isoforms. Angiogenesis. 2018 aug;21(3):545-555. https://doi.org/10.1007/s10456-018-9607-8

Author

Aanhane, Ed ; Schulkens, Iris A. ; Heusschen, Roy ; Castricum, Kitty ; Leffler, Hakon ; Griffioen, Arjan W. ; Thijssen, Victor L. / Different angioregulatory activity of monovalent galectin-9 isoforms. I: Angiogenesis. 2018 ; Vol. 21, Nr. 3. s. 545-555.

RIS

TY - JOUR

T1 - Different angioregulatory activity of monovalent galectin-9 isoforms

AU - Aanhane, Ed

AU - Schulkens, Iris A.

AU - Heusschen, Roy

AU - Castricum, Kitty

AU - Leffler, Hakon

AU - Griffioen, Arjan W.

AU - Thijssen, Victor L.

PY - 2018/8

Y1 - 2018/8

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Blood vessels

KW - Cancer

KW - Galectin

KW - Sprouting

KW - Tube formation

UR - http://www.scopus.com/inward/record.url?scp=85045069906&partnerID=8YFLogxK

U2 - 10.1007/s10456-018-9607-8

DO - 10.1007/s10456-018-9607-8

M3 - Article

VL - 21

SP - 545

EP - 555

JO - Angiogenesis

JF - Angiogenesis

SN - 0969-6970

IS - 3

ER -