Suppression of tumor progression in multiple myeloma by osteogenic microenvironment: Elucidation of the molecular pathogenesis of tumor suppressing niche

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16244
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: The University of Tokushima
• Principal Investigator: FUJII Shiro 徳島大学, 病院, 講師 (00618473)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 多発性骨髄腫 / 微小環境 / 細胞外小胞

Outline of Final Research Achievements

Multiple myeloma（MM）is an incurable hematopoietic malignancy which has an affinity for bone. MM develops exclusively in the bone marrow and generates destructive bone disease. While the bone formation was suppressed in the MM bone marrow environment, inverse correlation between the tumor suppressive effects and osteogenesis has been shown in MM patients with responder of novel agents such as proteasome inhibitors. In the present study, co-culture of MM cells with mature osteoblasts which were differentiated from bone marrow stromal cells induced MM cell death different from co-culture with MC3T3-El pre-osteoblasts. We also found that the reduction of IL-6 expression, the increase of osteoprotegerin and miR-125b were shown in mature osteoblasts derived from pre-osteoblasts which conferred to MM cell death.

Free Research Field

血液悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

骨髄腫細胞は骨芽細胞分化を抑制に自らの生存・増殖に好適な骨髄微小環境を形成していること、そして骨形成誘導により骨髄腫細胞の生存を許容しない排他的ニッチが形成され、骨量の回復と共に抗腫瘍活性を高める可能性が示唆された。骨芽細胞分化を基軸に骨髄腫骨髄微小環境内での各種細胞間でのmiRの移動や骨髄腫細胞の代謝制御が明らかになると新たな治療概念、治療戦略の構築に寄与すると考えられる。