Analysis of TGF-beta signaling in angiosarcoma and search for novel therapies

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20796
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Kumamoto University
• Principal Investigator: Sakamoto Ryoko 熊本大学, 大学院生命科学研究部(医), 特定研究員 (00965634)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 血管肉腫 / TGF-beta

Outline of Final Research Achievements

Analysis of the expression levels of various molecules associated with the TGF-β signaling pathway in angiosarcoma showed that although there were no significant differences in the phosphorylation of mad1/5 and Smad2/3, which accumulate in the nucleus and regulate gene transcription responses in angiosarcoma cell lines, the levels of TGF-β type II receptors and both ALK1 and ALK5 levels were significantly increased in angiosarcoma cell lines compared to normal vascular endothelial cells. Despite the decreased levels of TGF-β in the angiosarcoma cell lines, the results suggest an overreaction of the signaling pathway due to its stimulation; elucidation of the TGF-β signaling pathway may lead to novel therapies.

Free Research Field

Dermatology

Academic Significance and Societal Importance of the Research Achievements

血管肉腫は、標準治療が確立されておらず、難治性の肉腫である。進行例では、化学療法が主体となるが、未だ有効な治療法が確立されていない。そのために、血管肉腫に対する新規治療の開発は急務である。本研究は今回、血管肉腫におけるTGF-βシグナル伝達の解明することで、新たな治療方法の開発や奏功率の改善など治療応用についての可能性があるという側面もあり、学術的・社会的な意義を有している。