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Human trophoblast requires galectin-3 for cell migration and invasion

Bojić-Trbojević, ; Jovanović Krivokuća, M.; Vilotić, A.; Kolundžić, N.; Stefanoska, I.; Zetterberg, F.; Nilsson, U. J. LU ; Leffler, H. LU and Vićovac, Lj (2019) In Scientific Reports 9(1).
Abstract

Invasive extravillous cytotrophoblast of the human placenta expresses galectins-1, -3, and -8 in vivo and in vitro. This study aimed to investigate the potential role of galectin-3 in cell migration and invasion, using recombinant human galectin-3 (rhgalectin-3), small molecule galectin inhibitor I 47 , and galectin-3 silencing. HTR-8/SVneo cell migration was stimulated by rhgalectin-3 and reduced by I 47 , which could be neutralised by rhgalectin-3. Inhibitor specificity and selectivity for the galectins expressed in extravillous trophoblast were validated in solid phase... (More)

Invasive extravillous cytotrophoblast of the human placenta expresses galectins-1, -3, and -8 in vivo and in vitro. This study aimed to investigate the potential role of galectin-3 in cell migration and invasion, using recombinant human galectin-3 (rhgalectin-3), small molecule galectin inhibitor I 47 , and galectin-3 silencing. HTR-8/SVneo cell migration was stimulated by rhgalectin-3 and reduced by I 47 , which could be neutralised by rhgalectin-3. Inhibitor specificity and selectivity for the galectins expressed in extravillous trophoblast were validated in solid phase assays using recombinant galectin-1, -3, -8, confirming selectivity for galectin-3. HTR-8/SVneo cell migration and invasion, and invasion by isolated trophoblast cells in primary culture were significantly reduced in the presence of I 47, which could be restored by rhgalectin-3. Upon HTR-8/SVneo cell treatment with galectin-3 siRNA both LGALS3 and galectin-3 protein were dramatically decreased. Silencing of galectin-3 induced significant reduction in cell migration and invasion, which was restored by rhgalectin-3. The influence on known mediators of cell invasion, MMP2 and -9, and integrins α 1 , α 5 , and β 1 was followed in silenced cells, showing lower levels of MMPs and a large reduction in integrin subunit β 1 . These results show that galectin-3 acts as a pro-invasive autocrine/paracrine factor in trophoblast in vitro.

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organization
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publication status
published
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in
Scientific Reports
volume
9
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85061616715
ISSN
2045-2322
DOI
10.1038/s41598-018-38374-w
language
English
LU publication?
yes
id
682e520c-2b9a-43c3-a170-c4c97291e18a
date added to LUP
2019-02-25 10:17:14
date last changed
2019-03-27 04:39:17
@article{682e520c-2b9a-43c3-a170-c4c97291e18a,
  abstract     = {<p>                             Invasive extravillous cytotrophoblast of the human placenta expresses galectins-1, -3, and -8 in vivo and in vitro. This study aimed to investigate the potential role of galectin-3 in cell migration and invasion, using recombinant human galectin-3 (rhgalectin-3), small molecule galectin inhibitor I                             <sub>47</sub>                             , and galectin-3 silencing. HTR-8/SVneo cell migration was stimulated by rhgalectin-3 and reduced by I                             <sub>47</sub>                             , which could be neutralised by rhgalectin-3. Inhibitor specificity and selectivity for the galectins expressed in extravillous trophoblast were validated in solid phase assays using recombinant galectin-1, -3, -8, confirming selectivity for galectin-3. HTR-8/SVneo cell migration and invasion, and invasion by isolated trophoblast cells in primary culture were significantly reduced in the presence of I                             <sub>47,</sub>                              which could be restored by rhgalectin-3. Upon HTR-8/SVneo cell treatment with galectin-3 siRNA both LGALS3 and galectin-3 protein were dramatically decreased. Silencing of galectin-3 induced significant reduction in cell migration and invasion, which was restored by rhgalectin-3. The influence on known mediators of cell invasion, MMP2 and -9, and integrins α                             <sub>1</sub>                             , α                             <sub>5</sub>                             , and β                             <sub>1</sub>                              was followed in silenced cells, showing lower levels of MMPs and a large reduction in integrin subunit β                             <sub>1</sub>                             . These results show that galectin-3 acts as a pro-invasive autocrine/paracrine factor in trophoblast in vitro.                         </p>},
  articleno    = {2136},
  author       = {Bojić-Trbojević,  and Jovanović Krivokuća, M. and Vilotić, A. and Kolundžić, N. and Stefanoska, I. and Zetterberg, F. and Nilsson, U. J. and Leffler, H. and Vićovac, Lj},
  issn         = {2045-2322},
  language     = {eng},
  month        = {02},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Human trophoblast requires galectin-3 for cell migration and invasion},
  url          = {http://dx.doi.org/10.1038/s41598-018-38374-w},
  volume       = {9},
  year         = {2019},
}