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

人绒毛外滋养细胞表达分子在癌症侵袭调节机制中的作用

基本信息

批准号：
13671710
负责人：
HIGUCHI Toshihiro
金额：
$ 2.75万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671710/
关键词：
extravillous trophoblast cancer invasion DPP-IV chemokine ephrin 絨毛細胞浸潤癌浸潤癌転移

项目摘要

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

在胎盘早期，人类滋养细胞分化为绒毛外滋养细胞（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。尽管据报道EVT侵袭的机制与癌症侵袭相似，但EVT的侵袭仅限于子宫肌层内三分之一。我们之前分析了EVT侵袭的调控机制，发现EVT中表达的一些分子可能调节EVT对母体组织的侵袭。在调节EVT侵袭的分子中，我们发现CD9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，在这个项目中，我们研究了人类EVT中表达的分子对癌症侵袭调节机制的作用。首先，我们分析了女性盆腔器官和妇科癌症组织中人类 EVT 中表达的分子的表达。通过免疫组织化学和Northern印迹分析，在分泌期的人子宫内膜上皮细胞中表达了体外抑制EVT侵袭的二肽基肽酶IV（DPP-IV）。然而，DPP-IV在子宫内膜癌组织中的表达降低。此外，ephrin A1及其配体Eph酪氨酸激酶型受体均被发现在子宫内膜癌组织中表达。在这些分子中，DPP-IV 肽酶活性被发现可以抑制人绒癌衍生细胞系。随后的分析阐明，趋化因子RANTES的失活参与了DPP-IY的这种抗侵袭作用。结论是，在人类EVT中表达的一些分子，例如DPP-IV或ephrin/Eph系统，被发现在正常女性盆腔器官和妇科癌症中表达。对人类 EVT 中表达的这些分子的进一步研究可能会阐明癌症侵袭的调节机制。