Role of molecules expressed in human extravillous trophoblasts on the regulatory mechanism of cancer invasion

在胎盘形成早期，滋养层细胞分化为绒毛外滋养细胞（exfcravillous trophophlasts，EVT），侵入母体子宫组织，诱导母体螺旋动脉壁建立有效的胎盘循环。尽管报道EVT的侵袭机制类似于癌症的侵袭机制，但EVT的侵袭仅限于子宫肌层的内1/3。我们以前分析了EVT侵袭的调节机制，发现EVT中表达的一些分子可能调节EVT侵入母体组织。在调节EVT侵袭的分子中，我们发现CD 9抑制子宫内膜癌细胞系的侵袭。这一发现表明，调节EVT侵袭的分子也可能调节癌症侵袭。因此，在本项目中，我们研究了在人类EVT中表达的分子对癌症侵袭的调节机制的作用。首先，我们分析了表达的分子的表达， 关于我们 在女性盆腔器官和妇科癌症组织中的人EVT中。通过免疫组化和北方印迹分析，二肽基肽酶IV（DPP-IV），在体外抑制EVT的侵袭，表达在分泌期的人子宫内膜上皮细胞。而DPP-IV在子宫内膜癌组织中的表达明显降低。此外，Ephrin A1及其配体Eph酪氨酸激酶型受体在子宫内膜癌组织中均有表达。在这些分子中，发现DPP-IV肽酶活性抑制人胆管癌衍生细胞系。随后的分析表明，趋化因子RANTES的失活参与了DPP-IY的这种抗侵袭作用。总之，在人EVT中表达的一些分子，如DPP-IV或ephrin/Eph系统，在正常女性盆腔器官和妇科癌症中被发现表达。进一步研究这些分子在人EVT中的表达可能会阐明癌症侵袭的调节机制。

During early placentation, Human trophoblasts differentiate into exfcravillous trophohlasts (EVTs), which invade into maternal uterine tissue inducting walls of maternal spiral arteries to establish effective placental circulation. Although the mechanism of EVT invasion are reported to resemble to that of cancer invasion, invasion of EVT is limited to inner one third of uterine myometrium. We have previously analyzed regulatory mechanisms of EVT invasion, and found that some molecules expressed in EVTs might regulate the invasion of EVTs into maternal tissue. Among molecules which regulate EVT invasion, we have found that CD9 suppressed the invasion of uterine endometrial cancer cell line. This finding suggests that molecules which regulate EVT invasion might also regulate cancer invasion. Therefore in this project, we investigated the roles of molecules expressed in human EVTs on the regulatory mechanisms of cancer invasion. At first, we analyzed the expression of molecules expressed … More in human EVTs in female pelvic organ and in gynecological cancer tissues. By immunohistochemical and Northern blot analyses, Dipeptidyl peptidase IV (DPP-IV), which inhibits EVT invasion in vitro, was expressed in human endometrial epithelial cells of secretory phase. However, DPP-IV expression was decreased in endometrial carcinoma tissues. In addition, both ephrin A1 and its ligand Eph tyrosine kinase type receptor were found to expressed in endometrial cancer tissues. Among these molecules, DPP-IV peptidase activity was found to suppress human choriccarcinoma derived cell line. Subsequent analyses clarified that inactivation of chemokine RANTES is involved in this anti-invasive effect of DPP-IYIn conclusion, some molecules expressed in human EVTs such as DPP-IV or ephrin/Eph system were found to be expressed in normal female pelvic organ and gynecological cancer. Further investigation of these molecules expressed in human EVTs might clarify the regulatory mechanisms of cancer invasion Less