Inhibiting Bruton's Tyrosine Kinase to Counteract Chemoresistance and Stem Cell-Like Properties in Osteosarcoma

Osteosarcoma, a highly aggressive bone cancer, often develops resistance to conventional chemotherapeutics, leading to poor prognosis and survival rates. The malignancy and chemoresistance of osteosarcoma pose significant challenges in its treatment, highlighting the critical need for novel therapeu...

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Bibliographic Details
Published in:Environmental toxicology 2024-11, Vol.39 (11), p.4936-4945
Main Authors: Tsai, Hsiao-Chi, Lien, Ming-Yu, Wang, Shih-Wei, Fong, Yi-Chin, Tang, Chih-Hsin
Format: Article
Language:English
Subjects:
Aggressive behaviour
Angiogenesis
Bone cancer
Bruton's tyrosine kinase
Cancer
Cell migration
Chemoresistance
Cisplatin
Kinases
Malignancy
Medical prognosis
Osteosarcoma
Osteosarcoma cells
Stem cells
Tyrosine
Up-regulation
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Summary:Osteosarcoma, a highly aggressive bone cancer, often develops resistance to conventional chemotherapeutics, leading to poor prognosis and survival rates. The malignancy and chemoresistance of osteosarcoma pose significant challenges in its treatment, highlighting the critical need for novel therapeutic approaches. Bruton's tyrosine kinase (BTK) plays a pivotal role in B-cell development and has been linked to various cancers, including breast, lung, and oral cancers, where it contributes to tumor growth and chemoresistance. Despite its established importance in these malignancies, the impact of BTK on osteosarcoma remains unexplored. Our study delves into the expression levels of BTK in osteosarcoma tissues by data from the GEO and TCGA database, revealing a marked increase in BTK expression compared with primary osteoblasts and a potential correlation with primary site progression. Through our investigations, we identified a subset of osteosarcoma cells, named cis-HOS, which exhibited resistance to cisplatin. These cells displayed characteristics of cancer stem cells (CSCs), demonstrated a higher angiogenesis effect, and had an increased migration ability. Notably, an upregulation of BTK was observed in these cisplatin-resistant cells. The application of ibrutinib, a BTK inhibitor, significantly mitigated these aggressive traits. Our study demonstrates that BTK plays a crucial role in conferring chemoresistance in osteosarcoma. The upregulation of BTK in cisplatin-resistant cells was effectively countered by ibrutinib. These findings underscore the potential of targeting BTK as an effective strategy to overcome chemoresistance in osteosarcoma treatment.
ISSN:1520-4081
1522-7278
1522-7278
DOI:10.1002/tox.24368