Journal Article

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

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

2025

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/250/127/1213 / 631/67/1813 / Angiogenesis / Angiosarcoma / Cancer / Cell Line, Tumor / Cell Proliferation / Cells / Cytokine signaling / Cytokines / Dermatitis / Flow cytometry / Gene Expression Regulation, Neoplastic / Hemangioma / Hemangiosarcoma - genetics / Hemangiosarcoma - metabolism / Hemangiosarcoma - pathology / Humanities and Social Sciences / Humans / IL-13 receptor alpha2 / Interleukin 13 / Interleukin-13 - genetics / Interleukin-13 - metabolism / Interleukin-13 Receptor alpha2 Subunit - genetics / Interleukin-13 Receptor alpha2 Subunit - metabolism / Lymphocytes B / Malignancy / Medical prognosis / Metastasis / Microenvironments / multidisciplinary / Mutation / Neutrophils / Pathogenesis / Patients / Protein expression / Proteins / Sarcoma / Science / Science (multidisciplinary) / Signal Transduction / siRNA / Soft tissue sarcoma / STAT6 / Stat6 protein / Therapeutic targets / Transcriptomics / Tumor Microenvironment / Tumors / Vascular endothelial growth factor