RRC ID 86004
Author Saito H, Chan JY, Omori I, Iwasawa O, Sugimori A, Nakajima H, Ichimura R, Sato S, Sumida H.
Title IL-13/IL-13Rα2 axis promotes proliferation of angiosarcoma cells.
Journal Sci Rep
Abstract Angiosarcoma is a rare and aggressive soft tissue sarcoma with a poor prognosis and limited treatment options. The role of interleukin-13 (IL-13) and its receptors in angiosarcoma pathogenesis has been largely unknown. We first reanalyzed transcriptomic data from a published angiosarcoma cohort and found IL13RA2 mRNA elevated in angiosarcoma versus normal tissue. In addition, high IL13RA2 expression was significantly associated with increased nonsynonymous mutations. We next detected high IL-13 receptor α2 (IL-13Rα2) expression in angiosarcoma cell lines and patient samples compared to other cell types and benign vascular tumors. Moreover, histological analysis showed the presence of IL-13 in the angiosarcoma microenvironment. Functional studies using angiosarcoma cell lines, MO-LAS-B cells, revealed the promoting effect of IL-13 on cell proliferation. The effect was inhibited by siRNA-mediated knockdown of IL13RA2 or neutralizing antibodies against IL-13, suggesting the impact of IL-13/IL-13Rα2 axis in the angiosarcoma proliferation. In addition, IL-13 stimulation increased mRNA levels of IL13RA2 and VEGFA, suggesting an underlying positive feedback mechanism, which was attenuated by a STAT6 inhibitor. These findings highlight the importance of the IL-13/IL-13Rα2 axis in angiosarcoma progression and its potential as a novel therapeutic target for this challenging malignancy.
Volume 15(1)
Pages 31236
Published 2025-8-25
DOI 10.1038/s41598-025-15933-6
PII 10.1038/s41598-025-15933-6
PMID 40855097
PMC PMC12379233
MeSH Cell Line, Tumor Cell Proliferation Gene Expression Regulation, Neoplastic Hemangiosarcoma* / genetics Hemangiosarcoma* / metabolism Hemangiosarcoma* / pathology Humans Interleukin-13* / genetics Interleukin-13* / metabolism Interleukin-13 Receptor alpha2 Subunit* / genetics Interleukin-13 Receptor alpha2 Subunit* / metabolism Signal Transduction Tumor Microenvironment
IF 3.998
Resource
Human and Animal Cells A431(RCB0202)