Zhang Qian, Tan Dongmei, Luo Wenping, Lu Junjie, Tan Yi
Laboratory Animal Center, Chongqing Medical University, Chongqing, China.
PLoS One. 2012;7(6):e38487. doi: 10.1371/journal.pone.0038487. Epub 2012 Jun 5.
Well-controlled trophoblast invasion at maternal-fetal interface is a critical event for the normal development of placenta. CD82 is a member of transmembrane 4 superfamily, which showed important role in inhibiting tumor cell invasion and migration. We surmised that CD82 are participates in trophoblast differentiation during placenta development.
METHODOLOGY/PRINCIPAL FINDINGS: CD82 was found to be strongly expressed in human first trimester placental villous and extravillous trophoblast cells as well as in trophoblast cell lines. To investigate whether CD82 plays a role in trophoblast invasion and migration, we further utilized human villous explants culture model on matrigel and invasion/migration assay of trophoblast cell line HTR8/SVneo. CD82 siRNA significantly promoted outgrowth of villous explants in vitro (P<0.01), as well as invasion and migration of HTR8/SVneo cells (P<0.05), whereas the trophoblast proliferation was not affected. The enhanced effect of CD82 siRNA on invasion and migration of trophoblast cells was found associated with increased gelatinolytic activities of matrix metalloproteinase MMP9 while over-expression of CD82 markedly decreased trphoblast cell invasion and migration as well as MMP9 activities.
CONCLUSIONS/SIGNIFICANCE: These findings suggest that CD82 is an important negative regulator at maternal-fetal interface during early pregnancy, inhibiting human trophoblast invasion and migration.
母胎界面处滋养层细胞的良好调控性侵袭是胎盘正常发育的关键事件。CD82是跨膜4超家族的成员,在抑制肿瘤细胞侵袭和迁移中发挥重要作用。我们推测CD82参与胎盘发育过程中的滋养层细胞分化。
方法/主要发现:发现CD82在人孕早期胎盘绒毛和绒毛外滋养层细胞以及滋养层细胞系中强烈表达。为了研究CD82是否在滋养层细胞侵袭和迁移中发挥作用,我们进一步利用基质胶上的人绒毛外植体培养模型以及滋养层细胞系HTR8/SVneo的侵袭/迁移试验。CD82小干扰RNA显著促进体外绒毛外植体的生长(P<0.01),以及HTR8/SVneo细胞的侵袭和迁移(P<0.05),而滋养层细胞增殖未受影响。发现CD82小干扰RNA对滋养层细胞侵袭和迁移的增强作用与基质金属蛋白酶MMP9的明胶酶活性增加有关,而CD82的过表达显著降低滋养层细胞的侵袭和迁移以及MMP9活性。
结论/意义:这些发现表明,CD82是妊娠早期母胎界面处的重要负调节因子,抑制人滋养层细胞的侵袭和迁移。