β-1,4-galactosyltransferase III suppresses extravillous trophoblast invasion through modifying β1-integrin glycosylation

W. C. Liao, C. H. Liu, C. H. Chen, W. M. Hsu, Y. Y. Liao, H. M. Chang, C. T. Lan, M. C. Huang, M. K. Shyu

Research output: Contribution to journalArticle

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Abstract

Introduction Glycosylation controls diverse protein functions and regulates various cellular phenotypes. Trophoblast invasion is essential for normal placental development. However, the role of glycosylation in human placenta throughout pregnancy is still unclear. The β-1,4-galactosyltransferase III (B4GALT3) has been found to regulate cancer cell invasion. We therefore investigated the expression of B4GALT3 in placenta and its roles in trophoblast.

Methods B4GALT3 protein expression was examined by quantitative Western blotting analysis in human placentas. For identification of B4GALT3-positive cells in normal human placenta, immunohistochemistry and immunofluorescence methods were used. To investigate effects of B4GALT3 on extravillous trophoblast (EVT)-like cell and primary EVT cells, we analyzed cell growth, adhesion, migration, and invasion in mock and B4GALT3-transfected cell.

Results B4GALT3 expression significantly increased in third trimester human placenta. Immunostaining revealed that B4GALT3 expressed in placental villous cytotrophoblast, syncytiotrophoblast, and a subpopulation of EVT cells throughout pregnancy. Interestingly, we found increases in the expression level and percentage of B4GALT3-positive cells in third trimester EVT, but not in syncytiotrophoblasts and cytotrophoblasts of placental villi. Overexpression of B4GALT3 in HTR8/SVneo cells and primary trophoblast cells significantly suppressed cell migration. In addition, B4GALT3 suppressed cell invasion, and enhanced cell adhesion to laminin in HTR8/SVneo cells. Notably, we found that B4GALT3 modified glycans on β1-integrin, suppressed focal adhesion kinase (FAK) signaling, and enhanced β1-integrin degradation.

Discussion We propose that B4GALT3-mediated glycosylation change not only enhances β1-integrin binding to laminin, but also attenuates β1-integrin stability. Our findings suggest that B4GALT3 is a critical regulator for suppressing EVT invasion in the late stages of pregnancy.

Original languageEnglish
Pages (from-to)357-364
Number of pages8
JournalPlacenta
Volume36
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

Fingerprint

Galactosyltransferases
Trophoblasts
Glycosylation
Integrins
Placenta
Third Pregnancy Trimester
Laminin
Cell Adhesion
Pregnancy
Chorionic Villi
Placentation
Focal Adhesion Protein-Tyrosine Kinases
Cell Movement
Fluorescent Antibody Technique
Polysaccharides
Proteins

Keywords

  • B4GALT3
  • Extraillous trophoblast
  • Glycosylation
  • Integrin
  • Invasion
  • Placenta

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Reproductive Medicine
  • Developmental Biology

Cite this

β-1,4-galactosyltransferase III suppresses extravillous trophoblast invasion through modifying β1-integrin glycosylation. / Liao, W. C.; Liu, C. H.; Chen, C. H.; Hsu, W. M.; Liao, Y. Y.; Chang, H. M.; Lan, C. T.; Huang, M. C.; Shyu, M. K.

In: Placenta, Vol. 36, No. 4, 01.04.2015, p. 357-364.

Research output: Contribution to journalArticle

Liao, W. C. ; Liu, C. H. ; Chen, C. H. ; Hsu, W. M. ; Liao, Y. Y. ; Chang, H. M. ; Lan, C. T. ; Huang, M. C. ; Shyu, M. K. / β-1,4-galactosyltransferase III suppresses extravillous trophoblast invasion through modifying β1-integrin glycosylation. In: Placenta. 2015 ; Vol. 36, No. 4. pp. 357-364.
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AU - Liao, W. C.

AU - Liu, C. H.

AU - Chen, C. H.

AU - Hsu, W. M.

AU - Liao, Y. Y.

AU - Chang, H. M.

AU - Lan, C. T.

AU - Huang, M. C.

AU - Shyu, M. K.

PY - 2015/4/1

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N2 - Introduction Glycosylation controls diverse protein functions and regulates various cellular phenotypes. Trophoblast invasion is essential for normal placental development. However, the role of glycosylation in human placenta throughout pregnancy is still unclear. The β-1,4-galactosyltransferase III (B4GALT3) has been found to regulate cancer cell invasion. We therefore investigated the expression of B4GALT3 in placenta and its roles in trophoblast.Methods B4GALT3 protein expression was examined by quantitative Western blotting analysis in human placentas. For identification of B4GALT3-positive cells in normal human placenta, immunohistochemistry and immunofluorescence methods were used. To investigate effects of B4GALT3 on extravillous trophoblast (EVT)-like cell and primary EVT cells, we analyzed cell growth, adhesion, migration, and invasion in mock and B4GALT3-transfected cell.Results B4GALT3 expression significantly increased in third trimester human placenta. Immunostaining revealed that B4GALT3 expressed in placental villous cytotrophoblast, syncytiotrophoblast, and a subpopulation of EVT cells throughout pregnancy. Interestingly, we found increases in the expression level and percentage of B4GALT3-positive cells in third trimester EVT, but not in syncytiotrophoblasts and cytotrophoblasts of placental villi. Overexpression of B4GALT3 in HTR8/SVneo cells and primary trophoblast cells significantly suppressed cell migration. In addition, B4GALT3 suppressed cell invasion, and enhanced cell adhesion to laminin in HTR8/SVneo cells. Notably, we found that B4GALT3 modified glycans on β1-integrin, suppressed focal adhesion kinase (FAK) signaling, and enhanced β1-integrin degradation.Discussion We propose that B4GALT3-mediated glycosylation change not only enhances β1-integrin binding to laminin, but also attenuates β1-integrin stability. Our findings suggest that B4GALT3 is a critical regulator for suppressing EVT invasion in the late stages of pregnancy.

AB - Introduction Glycosylation controls diverse protein functions and regulates various cellular phenotypes. Trophoblast invasion is essential for normal placental development. However, the role of glycosylation in human placenta throughout pregnancy is still unclear. The β-1,4-galactosyltransferase III (B4GALT3) has been found to regulate cancer cell invasion. We therefore investigated the expression of B4GALT3 in placenta and its roles in trophoblast.Methods B4GALT3 protein expression was examined by quantitative Western blotting analysis in human placentas. For identification of B4GALT3-positive cells in normal human placenta, immunohistochemistry and immunofluorescence methods were used. To investigate effects of B4GALT3 on extravillous trophoblast (EVT)-like cell and primary EVT cells, we analyzed cell growth, adhesion, migration, and invasion in mock and B4GALT3-transfected cell.Results B4GALT3 expression significantly increased in third trimester human placenta. Immunostaining revealed that B4GALT3 expressed in placental villous cytotrophoblast, syncytiotrophoblast, and a subpopulation of EVT cells throughout pregnancy. Interestingly, we found increases in the expression level and percentage of B4GALT3-positive cells in third trimester EVT, but not in syncytiotrophoblasts and cytotrophoblasts of placental villi. Overexpression of B4GALT3 in HTR8/SVneo cells and primary trophoblast cells significantly suppressed cell migration. In addition, B4GALT3 suppressed cell invasion, and enhanced cell adhesion to laminin in HTR8/SVneo cells. Notably, we found that B4GALT3 modified glycans on β1-integrin, suppressed focal adhesion kinase (FAK) signaling, and enhanced β1-integrin degradation.Discussion We propose that B4GALT3-mediated glycosylation change not only enhances β1-integrin binding to laminin, but also attenuates β1-integrin stability. Our findings suggest that B4GALT3 is a critical regulator for suppressing EVT invasion in the late stages of pregnancy.

KW - B4GALT3

KW - Extraillous trophoblast

KW - Glycosylation

KW - Integrin

KW - Invasion

KW - Placenta

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