2002 Fiscal Year Final Research Report Summary
Role of molecules expressed in human extravillous trophoblasts on the regulatory mechanism of cancer invasion
| Project/Area Number |
13671710
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kyoto University |
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Principal Investigator |
HIGUCHI Toshihiro KYOTO UNIVERSITY, Graduate school of Medicine, Assistant, 医学研究科, 助手 (00283614)
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| Co-Investigator(Kenkyū-buntansha) |
FUJII Shingo KYOTO UNIVERSITY, Graduate school of Medicine, Professor, 医学研究科, 教授 (30135579)
FUJITA Jun KYOTO UNIVERSITY, Graduate school of Medicine, Professor, 医学研究科, 教授 (50173430)
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| Project Period (FY) |
2001 – 2002
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| Keywords | extravillous trophoblast / cancer invasion / DPP-IV / chemokine / ephrin |
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| Research Abstract |
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
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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-IY
In 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
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