Endoglin as therapeutic target in angiosarcoma.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08675
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kumamoto University
• Principal Investigator: Kajihara Ikko 熊本大学, 大学院生命科学研究部(医), 助教 (90433036)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: angiosarcoma / endoglin / TGF-beta

Outline of Final Research Achievements

Endoglin acts as a coreceptor for TGF-b signaling and is overexpressed in tumor-associated endothelial cells and enhances tumor angiogenesis. Here, we investigated the role of endoglin in the pathogenesis of angiosarcoma and whether endoglin inhibition results in antitumor activity. Endoglin was overexpressed in angiosarcoma, and its inhibition was effective in promoting apoptosis and the suppression of migration, invasion, tube formation, and Warburg effect in angiosarcoma cells. Knockdown of endoglin activated caspase 3/7 that is essential for apoptosis, reduced survivin levels, and decreased paxillin and vascular endothelial cadherin phosphorylation and matrix metalloproteinase 2 and matrix metalloproteinase 9 activities in angiosarcoma cells. Although endoglin is a coreceptor that regulates TGF-b signaling, the antitumor effect of endoglin in angiosarcoma was not based on Smad signaling regulation but on non-Smad TGF-b signaling.

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。今回、endoglin阻害による血管肉腫の抗腫瘍効果およびその分子メカニズムを解明した。