Low molecular mass polypeptide-2 in human trophoblast: over-expression in hydatidiform moles and possible role in trophoblast cell invasion.
Embryo implantation involves invasion of placental extravillous trophoblast cell (EVTs) into the uterus. Hyperactive EVT invasion occurs in hydatidiform moles and choriocarcinomas. We have previously demonstrated that the 20S proteasome is involved in mouse embryo implantation and its action is mediated via regulating the expression and activities of matrix metalloproteinase (MMP)-2 and MMP-9 in the EVTs. Our objective was to investigate whether low molecular mass polypeptide-2 (LMP2), a beta subunit of the 20S proteasome, is involved in the regulation of human trophoblast invasion. Normal human placentas or placentas from hydatidiform mole patients were collected and the expression of LMP2 in different cell types including trophoblastic column (TC), cytotrophoblast cells (CTB) and syncytiotrophoblast (STB) under different pathological states were studied by immunohistochemical analysis. Furthermore, the effect of LMP2 or proteasome on cell invasion was measured by using RNAi and inhibitors in a Matrigel invasion assay system in HTR-8/SVneo cells, a human invasive extravillous trophoblast cell line. Changes in the invasion-related molecules including MMP-2 and MMP-9 were also examined by using real time PCR and gelatin zymography. We demonstrated that the expression of LMP2 in TC of partial hydatidiform mole and complete hydatidiform mole, is higher than that in TC of normal human placentas. Besides, LMP2 knockdown significantly attenuated IL-1beta-induced cell invasion in vitro, a response readily induced by proteasome inhibitors. In summary, over-expression of the 20S proteasome beta-subunit LMP2 in trophoblast cells of hydatidiform moles may contribute to its highly invasive phenotype.
Fu
J-J
JJ
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Chaoyang District, Beijing 100101, China.
Lin
P
P
Lv
X-Y
XY
Yan
X-J
XJ
Wang
H-X
HX
Zhu
C
C
Tsang
B K
BK
Yu
X-G
XG
Wang
H
H
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D010064:Embryo Implantation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D006828:Hydatidiform Mole / Q000201:enzymology* / Q000473:pathology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D010929:Placentation / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D034622:RNA Interference; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D014594:Uterine Neoplasms / Q000201:enzymology* / Q000473:pathology
D015853:Cysteine Proteinase Inhibitors; D053583:Interleukin-1beta; D007976:Leupeptins; C067713:lactacystin; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D000111:Acetylcysteine