| Project/Area Number |
17K14981
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Tumor biology
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
Okita Yukari 筑波大学, 医学医療系, 助教 (30743710)
|
|---|
| Research Collaborator |
Kato Mitsuyasu
|
|---|
| Project Period (FY) |
2017-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | GPNMB / 乳がん / がん幹細胞 / EMT / 特殊環状ペプチド / 抗体 / 幹細胞マーカー / 環状ペプチド / 腫瘍形成 / 転移形成 / 上皮間葉転換 / 分子標的治療 |
|---|
| Outline of Final Research Achievements |
Cancer tissue is recognized as heterogeneous, and it contains a small proportion of cancer stem cells (CSCs), which is thought to be the root cause of cancer metastasis and relapse. Glycoprotein NMB (GPNMB) is a transmembrane protein, which highly expressed in many types of cancers including breast cancer, especially aggressive triple-negative type. Previously we showed that GPNMB contributes to breast cancer initiation and progression through induction of epithelial-mesenchymal transition (EMT). In this study, we found that GPNMB is exposed on the cell surface and induces CSC-like properties in breast cancer cells. Furthermore, we identified the important region in the extracellular domain, kringle-like domain (KLD), for its tumorigenic potential. Therefore, we believe that GPNMB and/or KLD of GPNMB should be promising target for cancer therapy.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究課題によりGPNMBが、がん幹細胞性特性の誘導に関与していることが示された。またGPNMBによる腫瘍形成誘導には、細胞外領域に位置するKrigle-like domain（KLD）が重要であることが初めて明らかになった。
がん幹細胞は治療後の再発や転移の原因になると考えられている。そのため、がん幹細胞に特異的な因子が解明できれば、それを標的としたがんの根本的な治療が可能になると期待される。そのため、本研究課題により得られた新規知見をもとに、GPNMBを標的とした新規がん治療薬が開発に成功すれば、その意義は学術的にも社会的にも大きい。
|
