| Project/Area Number |
17K07159
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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 |
Tumor biology
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| Research Institution | Kanazawa University |
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Principal Investigator |
Sasaki Soichiro 金沢大学, がん進展制御研究所, 助教 (50583473)
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| Co-Investigator(Kenkyū-buntansha) |
向田 直史 金沢大学, がん進展制御研究所, 教授 (30182067)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 乳がん / 骨転移 / Bone metastasis / 腫瘍学 / 浸潤・転移 |
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| Outline of Final Research Achievements |
From a murine triple negative breast cancer cell line, 4T1, we established a subclone, 4T1.3, which can metastasize to bone upon its injection into orthotopically. Using this model, we reported that 4T1.3 cells induced the intra-bone accumulation of fibroblasts. We assumed that fibroblasts in bone could supply a growth factor for cancer cells expressing a corresponding receptor.
Comprehensive gene expression analysis detected enhanced expression of a certain receptor and its cognate ligand in 4T1.3 cells and fibroblasts at bone metastasis sites, respectively.
The receptor gene deletion in 4T1.3 cells reduced their capacity to form intraosseous tumors while the receptor gene transduction into 4T1 cells enhanced their capacity to form intraosseous tumors. Even after bone metastatic foci developed, inducible suppression of the receptor molecule expression suppressed metastasis formation. Thus, we identified a candidate molecule as a target for bone metastasis of breast cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
骨転移は進行期の乳がん患者に好発し、生命予後を著しく低下させるが、骨転移に対する現行の治療法は対症療法に留まり、腫瘍細胞に直接作用する新たな治療法の開発が強く望まれている。
我々は骨内の乳がん細胞選択的に発現が亢進する受容体分子を見出し、同分子はヒト乳がん患者の骨転移巣でも発現が認められた。さらに、受容体分子の発現亢進は乳がん細胞株の骨内増殖能を促進させ、発現の欠失は骨内増殖能を著しく減弱させた。
本研究より骨転移巣におけるがん増殖に対する新たな受容体分子の関与が明らかとなった。この成果より、骨内のがん細胞の増殖そのものを抑制するという新たなコンセプトに基づいたがん骨転移治療法の開発が期待される。
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