| Project/Area Number |
10671134
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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 |
General surgery
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| Research Institution | KEIO UNIVERSITY |
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Principal Investigator |
IKEDA Tadashi Department of surgery, KEIO UNIVERSITY, Assistant professor, 医学部・外科学, 専任講師 (70124930)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAYAMA Shin Department of surgery, KEIO UNIVERSITY, Assistant, 医学部・外科学, 助手 (60296605)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | human breast cancer / bone metastasis / Integrin α_vβ_3 / Flowcytometry / nude rat model / echistatin / RGD tripeptide / RT-PCR / インテブリンα_Vβ_3 / 乳癌骨転移 / 接着因子 / インデブリンαvβ3 / インテグリンαvβ3 |
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| Research Abstract |
Integrin α_vβ_3 is expressed only in limited number of cell types such as some tumor cells and osteoclast. Breast cancer is characterized by frequent bone metastasis with dominant bone resorption. Only osteoclast is capable to resorb bone matrix and activation of osteoclast is essential for establishment of bone metastasis. In present study, we examined the expression of α_vβ_3 in breast cancer cells as to bone metastasis. Over-expression of α_vβ_3 was shown in both human breast cancer cell lines : MDA-MB-231 and MDA-MB-435, but not in MKL-4 with immunohistochemical study. Flowcytometry study showed the similar results (α_vβ_3 was detected in 82%, 92% of MDA-MB-231 and MDA-MB-435 cells, respectively, and 26% of MKL-4). Using breast cancer tissues, over-expression of α_vβ_3 was recognized 58% of patients (11/19) with bone metastasis while 39% of patients (7/18) without bone metastasis. Interestingly, the blockade of α_vβ_3 with echistatin (RGD tripeptide) prevented from metastasizing to bone in vivo. In our nude rat model, echistatin treatment (20 ug/kg/min) animals demonstrated bone metastasis 1.1±1.3 sites/rat, compared to control animals 4.0±0 sites/rat. Also the area of bone metastasis in animals with echistatin treatment was 0.6±1.2 mm^2 compared to 2.8±1.6 mm^2 with control animals. Integrin α_vβ_3 as therapeutic targets in bone metastasis of breast cancer has been suggested.
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