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.