Language
English
Publication Date
6-1-2025
Journal
Journal of Bone Oncology
DOI
10.1016/j.jbo.2025.100690
PMID
40502679
PMCID
PMC12158615
PubMedCentral® Posted Date
5-23-2025
PubMedCentral® Full Text Version
Post-print
Abstract
The CXCL10-CXCR3 axis regulates immunity, tumorigenesis, and metastasis in multiple cancers. Yet, its roles in osteosarcoma (OS), the predominant pediatric malignant bone tumor, are not fully defined. Our prior work has shown that elevated serum CXCL10 levels correlate with poor OS prognosis. The current study delves deeper by investigating how CXCL10-mediated CXCR3 signaling influences OS growth and metastatic spread. In vitro, CXCL10 and related CXCR3 ligands (CXCL4, CXCL9, and CXCL11) enhanced OS tumor cell migration. In an orthotopic xenograft mouse model with a newly created CXCR3 knockout (KO) mutant, tumor growth and lung metastasis decreased significantly when compared with the parental cell line. Transfecting the transcript isoform CXCR3A, but not CXCR3B, into KO cells restored metastatic phenotypes in mice, highlighting isoform specificity. Pharmacological CXCR3 inhibition reduced OS cell migration in vitro and metastasis in vivo. Mechanistically, CXCL10 triggered AKT (S473) and PAK1 (S144) phosphorylation in OS cell lines, but not in the KO mutant, implicating the role of these kinases in CXCL10-mediated metastasis. Collectively, our data indicate the CXCL10-CXCR3 axis as a key metastatic driver in OS, suggesting CXCR3 as a viable therapeutic target for treating OS metastasis.
Keywords
AKT, CXCL10, CXCR3, Metastasis, Osteosarcoma, PAK1
Published Open-Access
yes
Recommended Citation
Gyau, Benjamin B; Wang, Junyan; Chen, Xiang; et al., "The Metastatic Role of the CXCL10-CXCR3 Axis and Its Therapeutic Potential in Osteosarcoma" (2025). Faculty, Staff and Students Publications. 5294.
https://digitalcommons.library.tmc.edu/baylor_docs/5294
Graphical Abstract