Avoidance of milk fat globule-epidermal growth factor-8 (MFG-E8) tumor immunity via regulatory B cells and application of mechanism for colon cancer therapy
| Project/Area Number |
17K09383
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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 |
Gastroenterology
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| Research Institution | Shimane University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
石原 俊治 島根大学, 学術研究院医学・看護学系, 教授 (80263531)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 腫瘍免疫 / 腸管免疫 / 制御性B細胞 / MFG-E8 / IL-10 / 制御性B細胞（Breg） / 大腸癌治療 / MHG-E8 / 制御性B細胞（Breg) |
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| Outline of Final Research Achievements |
We have reported that milk fat globule-epidermal growth factor-8 (MFG-E8) promotes tumor growth and has a high level of expression in human colon cancer cells. Furthermore, regulatory B cells (Bregs) dysfunction associated with inflammatory bowel disease was found to lead to inflammation exacerbation. However, no mechanism for avoiding MFG-E8 tumor immunity via Bregs has been elucidated. In this study, Bregs number in MFG-E8 knockout (KO) mice was decreased, while CpG DNA-induced IL-10 production was significantly reduced in B cells obtained from those mice. These results suggest an important role of MFG-E8 in Bregs development and differentiation. Unfortunately, MFG-E8 KO mice showed unfavorable reproduction, and experiments focused on tumor incidence and inhibition with colitis-associated cancer model mice did not achieve favorable results. Accelerated Bregs function induced by MFG-E8 may impact development and promotion of colon cancer by inhibiting host tumor immunity.
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| Academic Significance and Societal Importance of the Research Achievements |
今回のMFG-E8 ノックアウト（KO）マウスを用いた研究では、MFG-E8が制御性B細胞（Breg）の発生や分化に重要な役割を果たしていることが明らかとなった。炎症性大腸癌モデルにおける大腸発癌と癌進展抑制に関しては期待した成果は上げることは出来なかったが、MFG-E8によるBregの活性化や機能促進は宿主の腫瘍免疫抑制を介して、大腸癌の発生や進展に影響する可能性があると考えられた。今後、腫瘍に対する免疫療法の新規開発につながる可能性があると思われた。
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Report
(5 results)
Research Products
(22 results)
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[Journal Article] Capabilities of fecal calprotectin and blood biomarkers as surrogate endoscopic markers according to ulcerative colitis disease type2019
Author(s)
Sonoyama H, Kawashima K, Ishihara S, Kotani S, Fukuba N, Oka A, Kusunoki R, Tada Y, Mishima Y, Oshima N, Moriyama I, Yuki T, Onishi K, Kinoshita Y
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Journal Title
J Clin Biochem Nutr
Volume: in press
NAID
Related Report
Peer Reviewed
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