Reactive oxygen species play roles in multiple myeloma pathogenesis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07178
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Sapporo Medical University
• Principal Investigator: Kohichi Takada 札幌医科大学, 医学部, 講師 (90398321)
• Co-Investigator(Kenkyū-buntansha): 加藤 淳二 札幌医科大学, 医学部, 教授 (20244345) ; 在原 洋平 札幌医科大学, 医学部, 研究員 (30749586)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 多発性骨髄腫 / STEAP1 / 活性酸素種 / 転移 / 浸潤 / 骨髄ホーミング

Outline of Final Research Achievements

Six-transmembrane epithelial antigen of the prostate 1 (STEAP1), identified in prostate cancer cells as a cell surface protein, is over-expressed in a subset of human cancers. In cases of Ewing sarcoma, STEAP1 augmented cell proliferation and invasion and was accompanied by increased reactive oxygen spices (ROS) levels. Here, we characterized the biological impact of STEAP1 and ROS in multiple myeloma (MM) pathogenesis. STEAP1 expression negatively correlated with OS as determined from a publicly accessible gene expression profile data set. A loss-of-function approach in cultured MM cell lines revealed that STEAP1 silencing suppressed migration, invasion and bone marrow homing through inhibition of ROS production. Mechanistically, the inhibition of STEAP1 was associated with increased expression of anti-oxidant molecules regulated by the transcription factor, nuclear erythroid 2-related factor (NRF2), in MM cells. This study identified STEAP1 as a therapeutic target for MM.

Free Research Field

臨床腫瘍

Academic Significance and Societal Importance of the Research Achievements

当該研究は，解析されていないSTEAP1-ROSがMMの転移・浸潤，ならびに骨髄ホーミングに関与していることを明らかにした．MM細胞のROS産生低下を誘導可能な薬剤としてSTEAP1抑制薬あるいはNRF2賦活剤がMMの治療薬として有用である可能性が示唆された．以上より，新規MM治療薬開発に貢献でき，臨床的意義が高い．さらに，同研究成果はさまざまな癌腫にも応用可能であり，本研究の社会貢献度は大きいと思われる．