Hyaluronan, CD44 and its variant exons in human trophoblast invasion and placental angiogenesis
Hyaluronan, CD44 and its variant exons in human trophoblast invasion and placental angiogenesis
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DOI：
10.1093/molehr/2.9.685
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发表时间：
1996-09-01
影响因子：
4
通讯作者：
Stern, Robert
中科院分区：
文献类型：
--
作者：
Goshen, Ran;Ariel, Ilana;Stern, Robert
透明质酸和它的一种受体CD44在早期人类受孕和胎盘基质中都有表现。由可变外显子剪接引起的CD44变异在转移性人类恶性肿瘤中发现，并且也参与透明质酸的摄取和降解。由此产生的透明质酸片段被认为是高度血管生成的。我们假设滋养细胞侵袭子宫蜕膜的自我限制过程部分是由于CD44的选择性剪接策略，类似于侵袭性癌细胞在转移扩散和可能的血管生成过程中使用的策略。研究人员使用CD44s和转移性肿瘤进展过程中表达的外显子CD44v7特异性单克隆抗体来检验这一假设。在这项研究中，我们首次发现人类滋养细胞表达CD44。妊娠早期和中期的中间滋养细胞表现出CD44的标准形式，而负责胎盘侵入特征的外滋养细胞则表现出CD44v7-8的选择性剪接形式。此外，在增生性胎盘的情况下，肌层上的纤维蛋白层中嵌入的滋养细胞有明显的膜染色。高转移性绒毛膜癌细胞也表达CD44v7-8。因此，我们提出，入侵的滋养细胞利用交替剪接机制。这些细胞通过携带CD44v7-8异构体通过允许的ECM保持其侵袭能力，CD44v7-8异构体与透明质酸弱结合，从而防止透明质酸被细胞内透明质酸酶降解。
Both hyaluronan and one of its receptors, CD44, can be demonstrated in the early human conceptus and in placental stroma. The variants of CD44 resulting from variable exon splicing are found in metastasizing human malignancies and are also involved in hyaluronan uptake and degradation. The resulting hyaluronan fragments are known to be highly angiogenic. We postulated that the self-limited process of trophoblast invasion of the uterine decidua results in part from the strategy of alternative splicing of CD44, similar to that used by invasive cancer cells in the course of metastatic spread and possibly angiogenesis. Monoclonal antibodies specific for CD44s and for an exon expressed during metastatic tumour progression, CD44v7, were used to examine this hypothesis. In this study we found human trophoblasts, for the first time, to express CD44. Intermediate trophoblasts of first and second trimester exhibited the standard form of CD44 while extravillous trophoblasts, which are responsible for the invading characteristics of the placenta, were positive for the alternatively spliced form, the CD44v7-8. Moreover, in the case of placenta accreta there was a prominent membrane staining of the trophoblasts that were embedded in the fibrin layer over the myometrium. The highly metastatic choriocarcinoma cells also expressed CD44v7-8. We propose, therefore, that the invading trophoblasts utilize the alternatively splicing machinery. These cells retain their invasive capabilities through the permissive ECM by carrying the CD44v7-8 isoform, which binds weakly to hyaluronan and thus prevents it from being degraded by intracellular hyaluronidase.