Roles of GPNMB in cancer stem cells and development of therapeutic agent targeting GPNMB

2018 Fiscal Year Final Research Report

• 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
• Keywords: GPNMB / 乳がん / がん幹細胞 / EMT / 特殊環状ペプチド / 抗体

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.

Free Research Field

腫瘍生物学、実験病理学

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。