| Project/Area Number |
16K10479
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Nippon Medical School |
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Principal Investigator |
Wada Ryuichi 日本医科大学, 医学部, 准教授 (20260408)
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| Co-Investigator(Kenkyū-buntansha) |
坂谷 貴司 日本医科大学, 医学部, 教授 (50431903)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 乳癌 / HER2 / スプライスバリアント / 増殖 / 幹細胞 / breast cancer / splice variant / isoform / stem cell / proliferation / delta-HER2 / 2量体 / 細胞増殖 / 転移 / Breast cancer / 癌幹細胞 |
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| Outline of Final Research Achievements |
The association of expression of delta-HER2, a splice variant of HER2, and cancer stem cell was investigated in culture cells and human HER2-positive breast cancers. The overexpression of delta-HER2 in culture cells suppressed the proliferation of the cell. In human HER2-positive breast cancers, the cells expressing delta-HER2 was scattered in the cancer tissue. Most of the cells positive for delta-HER2 were negative for Ki-67, and the cells were closely associated with the cells positive for a cancer stem cell marker, aldehyde dehydrogenase 1 (ALDH1). It was considered that the expression delta-HER2 was associated with cancer stemness, and the delta-HER2-expressing cells may be a therapeutic target of HER2-positive breast cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
HER2は増殖と癌化に重要な役割を果たしていると考えられているが、癌幹細胞化との関わりを明らかにすることで、悪性腫瘍の病態の理解へつながる。現在のところ、癌の幹細胞化を念頭に置いた治療法は存在しない。HER2を標的とした分子標的治療は実用化されているが、delta-HER2を標的として幹細胞化の抑制から転移を抑制する治療法も可能であろう。このような転移の抑制という治療戦略は、比較的若い患者の多い乳癌の長期予後を改善するうえで重要な治療戦略となる可能性がある。また、胃癌の約20%においてもHER2の過剰発現が見られ、胃癌の治療に対する応用も期待される。
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