Survival mechanism of breast cancer cells in the bone microenvironment at the latent stage of bone metastasis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07619
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Yamagata University
• Principal Investigator: Futakuchi Mitsuru 山形大学, 医学部, 教授 (60275120)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 骨微小環境 / 乳がん / 骨転移 / がん幹細胞

Outline of Final Research Achievements

Transforming growth factor-beta (TGF-beta) plays a key role in bone metastasis formation; we hypothesized the possible involvement of TGF-beta in the induction of cancer stem cells (CSCs) in the bone microenvironment (micro-E), which may be responsible for chemo-resistance. We found treatment with R1-Ki decreased tumor volume and cell proliferation in the bone micro-E. The number of cells positive for the CSC markers, SOX2, and CD166 in the bone micro-E, were significantly higher than those in the subQ micro-E. R1-Ki treatment significantly decreased the number of CSC marker positive cells in the bone micro-E but not in the subQ micro-E. Our results indicated that the bone micro-E is a key niche for CSC generation, and TGF-beta signaling has important roles in generating CSCs and tumor cell proliferation in the bone micro-E.

Free Research Field

がんの微小環境

Academic Significance and Societal Importance of the Research Achievements

本研究では、１）骨微小環境に特異的なCSCに発現する因子を同定すること、同定された因子の機能を解析し治療抵抗性への関与を検索することで、２）皮下微小環境のCSCが骨微小環境のCSCと変化し治療抵抗性を示すメカニズムの解析をした。本研究は、微小環境に特異的ながん幹細胞のprimary cultureを単離し、独自に開発した動物モデルで治療抵抗性への関与を明らかにする独創的な研究である。本研究の成果に基づき、骨微小環境に潜むがん幹細胞（顕在化前の微小骨転移）を検出が可能となり、原発巣治療後の再発および転移を防ぐ治療法を創造することができる。