Role of osteocytes in the progression of malignant tumors with bone lesions

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K21016
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: The University of Tokushima
• Principal Investigator: TANIMOTO Kotaro 徳島大学, 病院, 診療支援医師 (90908188)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 骨細胞 / がんと骨病変

Outline of Final Research Achievements

The progression of tumors developing in bone is closely related to the bone marrow microenvironment (niche). Osteocytes comprise the majority of bone cells and play a central role in the regulation of the bone marrow niche. In multiple myeloma, malignancy of the plasma cells forming destructive bone lesions, apoptosis of osteocytes is observed with tumor progression. However, its pathological significance remains unclear. In this study, we developed a unique mouse myeloma cell line allogeneic transplantation model that can specifically induce apoptosis of osteocytes in vivo. Using this model, we demonstrated that apoptosis of osteocytes promotes myeloma growth and metastasis. These results are expected to provide the basis for establishing a new treatment strategy for myeloma and other bone cancers by preventing apoptosis of osteocytes.

Free Research Field

骨代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究は、骨細胞のアポトーシスを防ぐことで骨への骨髄腫や他のがんの骨転移・進展を阻止し、予防する新規治療法を確立する可能性を示すものである。また、本研究で確立したVk12598骨髄腫細胞株は正常免疫を有する同種移植が可能であり、Dmp1-HBEGFマウスと組み合わせることで、経時的にその進行や進展部位をモニターすることができ、骨細胞のがん病態での役割やがん免疫に対する役割を解析できる独自性の高い動物モデルであった。骨細胞のアポトーシスによって誘導される候補分子を抽出したため、今後骨細胞特異的遺伝子改変マウスを用いた更なる詳細なメカニズムの解明や新規治療法の開発につなげる予定である。