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<p>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 <i>IL13RA2</i> mRNA elevated in angiosarcoma versus normal tissue. In addition, high <i>IL13RA2</i> 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 <i>IL13RA2</i> 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 <i>IL13RA2</i> and <i>VEGFA</i>, 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.</p>

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IL-13/IL-13Rα2 axis promotes proliferation of angiosarcoma cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月25日

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  • Hinako Saito,
  • Jason Yongsheng Chan,
  • Issei Omori,
  • Okuto Iwasawa,
  • Ayaka Sugimori,
  • Hibari Nakajima,
  • Ryuzo Ichimura,
  • Shinichi Sato,
  • Hayakazu Sumida

摘要

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.