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Interleukin-24 inhibits the phenotype and tumorigenicity of cancer stem cell in osteosarcoma via downregulation Notch and Wnt/β-catenin signaling
Journal of Bone Oncology ( IF 3.1 ) Pub Date : 2021-11-03 , DOI: 10.1016/j.jbo.2021.100403
Baobiao Zhuo 1 , Xihua Wang 1 , Yang Shen 1 , Jiayong Li 1 , Shixian Li 1 , Yuan Li 1 , Rong Wang 2
Affiliation  

Osteosarcoma frequently presents as recurrence and metastasis, even if the primary lesion was eradicated and/or radiotherapy and chemotherapy were administered. Osteosarcoma cancer stem cells (CSCs) are one of the key factors for the recurrence and metastasis of osteosarcoma. We have shown that interleukin-24 (IL-24) inhibits osteosarcoma cell proliferation, migration and invasion in vitro. In the current study, we investigated the role of IL-24 in inhibiting the growth of osteosarcoma CSCs. IL-24 inhibited proliferation and invasion and decreased the stemness of osteosarcoma CSCs in vitro. In a nude mouse xenograft model, IL-24 significantly inhibited the growth of tumors originating from osteosarcoma CSCs. Moreover, we found that IL-24 was able to inactivate both Notch and Wnt/β-Catenin signaling, which are important for the development of the biological characteristics of CSCs. These data demonstrate that IL-24 is able to kill not only cancer cells but also CSCs in osteosarcoma, suggesting that IL-24 might eradicate osteosarcoma and enhance long-term cure rates in patients with osteosarcoma.



中文翻译:

Interleukin-24 通过下调 Notch 和 Wnt/β-catenin 信号通路抑制骨肉瘤中癌症干细胞的表型和致瘤性

骨肉瘤经常表现为复发和转移,即使原发病灶已被根除和/或进行了放疗和化疗。骨肉瘤癌干细胞(CSCs)是骨肉瘤复发和转移的关键因素之一。我们已经证明白细胞介素 24 (IL-24) 在体外抑制骨肉瘤细胞增殖、迁移和侵袭。在目前的研究中,我们研究了 IL-24 在抑制骨肉瘤 CSC 生长中的作用。IL-24 在体外抑制骨肉瘤 CSCs 的增殖和侵袭并降低其干性。在裸鼠异种移植模型中,IL-24 显着抑制源自骨肉瘤 CSC 的肿瘤的生长。此外,我们发现 IL-24 能够使 Notch 和 Wnt/β-Catenin 信号通路失活,这对 CSCs 生物学特性的发展很重要。这些数据表明,IL-24 不仅能够杀死骨肉瘤中的癌细胞,还能够杀死 CSC,表明 IL-24 可能根除骨肉瘤并提高骨肉瘤患者的长期治愈率。

更新日期:2021-11-08
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