2005 Fiscal Year Final Research Report Summary
Manufacture of novel RCAS1-targeting therapy against uterine cancer
| Project/Area Number |
16591669
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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 | KYUSHU UNIVERSITY |
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Principal Investigator |
SONODA KENZO Kyushu University, Graduate School of Medical Sciences, Department of Obstetrics and Gynecology, Research Associate, 大学病院, 助手 (30294929)
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| Project Period (FY) |
2004 – 2005
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| Keywords | RCAS1 / apoptosis / stromal tissue reaction / ELISA / ectodomain shedding / tumor growth / siRNA / molecular targeting therapy |
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| Research Abstract |
Objectives : RCAS 1 was reported to express strongly in uterine cancer and induce apoptosis in putative receptor expressing cells including peripheral lymphocytes. The objects of this study were to investigate 1) association between RCAS1 expression and invasive potency of cancer cells, 2) measurement of serum RCAS1 concentration in gynecologic cancer patients, and 3) secretion mechanism of RCAS1.
Results : 1) Association between RCAS1 expression and invasive potency of cancer cells. Immunohistochemistry was performed. In uterine cervical and endometrial cancer, significant association was shown with tumor RCAS1 expression and the expression of matrix metalloprotease-1 and laniinin-5 of tumor cells, and number of apoptotic lymphocytes in primary and metastatic lesions. Moreover, number of tumor stromal vimentin positive cells was inversely decreased with tumor cell RCAS1 expression. RCAS1 gene transfection experiments were performed. In vivo tumor growth was exaggerated when COS-7 cell,
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which was negative for RCAS1, was transfected with RCAS 1 gene. On the contrary, in vivo tumor growth was suppressed when SiSo cell, which was positive for RCAS1, was transfected with siRNA specific for RCAS1.
2) Measurement of serum RCAS1 concentration in gynecologic cancer patients. Serum RCAS1 concentration was measured by ELISA. As a result, RCAS1 value was significantly higher in uterine cancer patients than in healthy donors. Concerning uterine cervical cancer, RCAS1 value was significantly higher in adenocarcinoma than in squamous cell carcinoma. Additionally, RCAS1 value was related with size of tumor.
3) Secretion mechanism of RCAS1. SiSo cell, which was positive for RCAS1, was treated with phorbol ester with or without protease inhibitor, GM6001. After treatment of phorbol ester, RCAS1 expression was diminished on SiSo cell but secretion of RCAS1 was increased in cell culture supernatant. However, RCAS1 expression was not decreased when SiSo cell was treated with GM6001 followed by phorbol ester. Therefore, it was suggested that RCAS1 was secreted by ectodomain shedding.
Acquisition of data concerning the molecular mechanisms for RCAS1 function may allow us not only to detect uterine cancer but also to explore novel therapy by targeting RCAS1. Less
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