Roles of acetylated HMGB1 secreted from cancer cells in CRPC

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18142
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Hiroshima University
• Principal Investigator: Goto Keisuke 広島大学, 病院(医), 助教 (30784251)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: HMGB1 / Prostate cancer / Cancer microenvironment

Outline of Final Research Achievements

High mobidity group protein box 1 (HMGB1), a non-histone chromatin binding protein, is normally present in the nucleus. Under certain conditions, HMGB1 is in the cytoplasm and secreted into the extracellular space as the signal molecule. Overexpression of HMGB1 was significantly associated with pT stage, Gleason score. The patients with higher cytoplasmic HMGB1 had significantly worse prognosis after radical prostatectomy. HMGB1 silencing significantly reduced cell proliferation in PCa cells. To assess roles of secreted HMGB1 in cancer microenvironment, HMGB1 levels in periprostatic adipose tissue (PPAT) in patients who underwent radical prostatectomy was investigated. HMGB1 levels in PPAT were significantly higher in cases with higher Gleason score. These results suggested that HMGB1 was associated with PCa progression and cell proliferation, and secreted HMGB1 in cancer microenvironment had significant roles in PCa progression.

Free Research Field

泌尿器癌

Academic Significance and Societal Importance of the Research Achievements

前立腺周囲脂肪組織中のサイトカインの発現が前立腺癌の悪性度と関連することはこれまでにない発見であり、前立腺癌におけるがん微小環境との関連を明らかにするための重要な結果であると考えられる。また、HMGB1の関与するシグナルは前立腺癌のみならず他臓器の腫瘍においても同様に存在すると考えられ、本研究で得られた知見は他のあらゆる癌腫へ応用可能である。