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

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 detected high IL-13 receptor 2 (IL-13R2) 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 direct impact of IL-13/IL-13R2 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-13R2 axis in angiosarcoma progression and its potential as a novel therapeutic target for this challenging malignancy.