Glycodelin-A as a modulator of trophoblast invasion.
BACKGROUND
Trophoblast invasion is crucial to placentation. The relationship between decidual glycodelin-A and trophoblast invasion is not known.


METHODS
Invasiveness of First trimester extravillous cytotrophoblast-1 (TEV-1) cell line, TEV-1, cells was determined by trans-well invasion assay. The gene expression, protein secretion and activities of the matrix metalloproteinase (MMP)-2 and -9, urokinase plasminogen activator (uPA), tissue inhibitor of metalloproteinase (TIMP)-1 and -2 and plasminogen activator inhibitor (PAI-1) of glycodelin-A-treated cells were measured by quantitative PCR, ELISA and gel zymography, respectively.


RESULTS
Glycodelin-A bound to TEV-1 cells. At a concentration of 1 microg/ml, glycodelin-A, but not other glycodelin isoforms, suppressed the invasion of TEV-1 cells. The effect was glycosylation-dependent and was associated with reduction (P < 0.05) of MMP2, MMP9 and uPA activities in the conditioned medium from the treated culture. Glycodelin-A treatment suppressed the amount of MMP2 protein in the conditioned medium (P < 0.05) and MMP2 mRNA in the cells (P < 0.05), but did not affect that of MMP9. Glycodelin-A also significantly reduced the expression, secretion and activity of uPA (P < 0.05). The treatment did not affect the expression of TIMP-1, TIMP-2 or PAI-1, cell proliferation or survival of the cells.


CONCLUSIONS
Glycodelin-A inhibits the invasion of extravillous cytotrophoblasts mainly by suppressing the activity of MMP2 and MMP9 in a glycosylation-dependent fashion.
Lam
Kevin K W
KK
Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong SAR, China.
Chiu
Philip C N
PC
Chung
Man-Kin
MK
Lee
Cheuk-Lun
CL
Lee
Kai-Fai
KF
Koistinen
Riitta
R
Koistinen
Hannu
H
Seppala
Markku
M
Ho
Pak-Chung
PC
Yeung
William S B
WS
D002460:Cell Line; D005260:Female; D000071816:Glycodelin; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D010929:Placentation / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000502:physiology*; D011261:Pregnancy Trimester, First; D014327:Trophoblasts / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D000071816:Glycodelin; D006023:Glycoproteins; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9