Metabolomics analysis of plasma from patients with head hemangiosarcoma and elucidation of the mechanism of tumor growth

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16212
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kobe University
• Principal Investigator: Jimbo Haruki 神戸大学, 医学研究科, 医学研究員 (70896894)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 血管肉腫 / メタボロミクス / グルタミン酸 / glutaminase 1 / GLS1阻害剤

Outline of Final Research Achievements

Metabolomics (a method for comprehensive analysis of small molecular compounds) of plasma samples from patients with head angiosarcoma revealed elevated levels of L-glutamic acid. Considering the possibility that L-glutamate may be involved in the growth of angiosarcoma, we focused on glutaminase 1(GLS 1), the enzyme that converts L-glutamine to L-glutamic acid. The growth of a human angiosarcoma cell line was significantly inhibited by the addition of a GLS 1 inhibitor. To elucidate the mechanism, we comprehensively analyzed the altered mRNA expression in the cell line using microarrays. GLS immunostaining in tumor specimens from angiosarcoma patients was positive for tumor cells, but negative for normal vascular endothelial cells from the same specimens.

Free Research Field

医学(皮膚悪性腫瘍 尋常性白斑)

Academic Significance and Societal Importance of the Research Achievements

頭部血管肉腫は稀少な皮膚原発の悪性腫瘍であり、高齢者に生じやすく皮膚に生じる悪性腫瘍の中では最も予後が 悪い。
治療に関しては現行の化学療法(抗がん剤)では投与を継続するも薬剤耐性により再発する例が多く、新規薬剤の発見が待たれる状況である。本研究では、血管肉腫の腫瘍細胞ではGLS 1 の発現が亢進しGLS 1阻害剤により増殖が阻害されるという結果が得られたことから、GLS 1阻害剤が頭部血管肉腫の新規薬剤の候補の一つになる可能性が示唆された。