| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
In the present study, we examined the expression and function of the four cell-surface peptidases, aminopeptidase A (APA), neutral endopeptidase (NEP), dipeptidyl peptidase IV (DPPIV), and placental leucine aminopeptidase (P-LAP) in gynecologic cancer cells. APA, NEP, DPPIV and P-LAP were differentially expressed and localized in various gynecologic malignancies including cervical cancer, endometrial cancer, ovarian cancer and choriocarcinoma in a tumor-type specific pattern. The expression levels were up-regulated or down-regulated depending on histological grade or disease progression. These peptidases play regulatory roles in tumor cell proliferation, migration, invasion or angiogenesis via degradation/inactivation of target peptides such as angiotensin II, endothelin-1, some chemokines (e.g. SDF-1,RANTES) and oxytocin, which act on cancer cells as a stimulatory or inhibitory factor. Our in vivo studies using nude mouse xenograft models demonstrated that overexpression of APA, NEP or DPPIV suppressed the growth, metastasis, angiogenesis, and peritoneal dissemination of ovarian cancer or cervical cancer. In contrast, P-LAP overezpression in endometrial cancer significantly correlated with impaired patient prognosis and the resistance of cancer cells to chemotherapy. In conclusion, these peptidases may become not only a new diagnostic/prognostic marker, but also a novel molecular target for treatment of gynecologic malignancies.
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