Studies on the functions of IL-34 and its therapeutic application for multiple melanoma-relative osteolytic disease

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09913
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Hokkaido University
• Principal Investigator: Ishikawa Kozo 北海道大学, 遺伝子病制御研究所, 客員研究員 (20624795)
• Co-Investigator(Kenkyū-buntansha): 清野 研一郎 北海道大学, 遺伝子病制御研究所, 教授 (20312845)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 多発性骨髄腫 / 骨溶解病変 / IL-34 / 破骨細胞形成

Outline of Final Research Achievements

Multiple myeloma (MM) is a hematological malignancy and causes debilitating osteolytic disease. Interleukin-34 (IL-34), a ligand of CSF-1 receptor, might contribute to osteoclast differentiation. In this study, we identified IL-34 as an osteoclastogenic cytokine accelerates osteolytic disease in MM, which was enhanced by proinflammatory cytokines or bone marrow stromal cells. MM-derived IL-34 promoted osteoclast formation from mouse BM cells in vitro. Silencing of Il34 by small interfering RNA impaired osteoclast formation in vitro and attenuated osteolytic disease in vivo. In BM aspirates from MM patients, the expression levels of IL-34 in CD138+ populations vary among patients. MM-derived IL-34 promoted osteoclast formation from human monocytes, which was reduced by a neutralizing antibody against IL-34.
Taken together, this study describes MM-derived IL-34 may enhance osteolysis and suggesting IL-34 as a potential therapeutic target on osteoclastogenesis in MM patient.

Free Research Field

がん免疫療法

Academic Significance and Societal Importance of the Research Achievements

多発性骨髄腫は、高齢者の罹患率が高く骨破壊を主徴候とする造血器腫瘍の一つであるが、それに対する有効な治療薬が未だ開発されていない。我々は、腫瘍の増悪因子であるTAMの分化に関わり、幾つかの悪性腫瘍（肺癌、卵巣癌、腎臓癌など）の予後悪化への寄与が考えられるIL-34が、骨破壊病変に関与することを仮定し、実験系や臨床研究にて示した。このことは骨破壊病態に対する治療標的の開発として意義があると考える。