State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Endocrinology. 2009 Dec;150(12):5596-605. doi: 10.1210/en.2009-0570. Epub 2009 Oct 15.
Well-controlled trophoblast invasion into uterine decidua is a critical process for the normal development of placenta, which is tightly regulated by various factors produced within the trophoblast-endometrial microenvironment. CXCL14 is involved in tumor growth and metastasis, and its expression in placenta is temporally regulated during pregnancy. However, the role of CXCL14 in trophoblast function during human pregnancy is not clear. In this study, by using RT-PCR through human pregnancy, we found that CXCL14 was selectively expressed at early but not late pregnancy. Immunostaining revealed that CXCL14 proteins were strongly expressed in villous cytotrophoblasts and moderately in decidualized stromal cells but very weakly in syncytiotrophoblasts and extravillous trophoblasts. The effect of CXCL14 on trophoblast invasion were examined by using human villous explants cultured on Matrigel and further proved by invasion and migration assay of primary trophoblast cells and trophoblast cell line HTR-8/SVneo. Our data showed that CXCL14 significantly inhibited outgrowth of villous explant in vitro; this effect is due to suppression of trophoblast invasion and migration through regulating matrix metalloproteinases activities, whereas the trophoblast proliferation was not affected. Moreover, because a receptor for CXCL14 has not been identified, we performed further cell-specific CXCL14 binding activities with regard to different cell types within the maternal-fetal interface. Our data revealed that CXCL14 could specifically bind to trophoblast cells but not decidual cells from the maternal-fetal interface. These results suggest that CXCL14 plays an important role in regulating trophoblast invasion through an autocrine/paracrine manner during early pregnancy.
良好控制的滋养细胞侵入子宫蜕膜是胎盘正常发育的关键过程，这一过程受到滋养细胞-子宫内膜微环境中产生的各种因素的严格调节。CXCL14 参与肿瘤的生长和转移，其在胎盘组织中的表达在妊娠期间呈时间调节。然而，CXCL14 在人妊娠期间对滋养细胞功能的作用尚不清楚。在这项研究中，我们通过 RT-PCR 检测人类妊娠，发现 CXCL14 仅在妊娠早期选择性表达，而不在妊娠晚期表达。免疫染色显示，CXCL14 蛋白在绒毛滋养细胞中强烈表达，在蜕膜化基质细胞中中度表达，但在合体滋养细胞和绒毛外滋养细胞中表达非常弱。我们通过在 Matrigel 上培养人绒毛外植体来检测 CXCL14 对滋养细胞侵袭的影响，并通过原代滋养细胞和滋养细胞系 HTR-8/SVneo 的侵袭和迁移实验进一步证明了这一点。我们的数据表明，CXCL14 显著抑制了绒毛外植体的体外生长；这种作用是由于抑制了滋养细胞的侵袭和迁移，通过调节基质金属蛋白酶的活性，而不会影响滋养细胞的增殖。此外，由于尚未鉴定出 CXCL14 的受体，我们针对母体-胎儿界面内的不同细胞类型进行了细胞特异性 CXCL14 结合活性研究。我们的数据表明，CXCL14 可以特异性结合滋养细胞，但不能结合母体-胎儿界面的蜕膜细胞。这些结果表明，CXCL14 通过自分泌/旁分泌方式在妊娠早期发挥重要作用，调节滋养细胞的侵袭。
