Protumor effect of CXCL10/CXCR3 axis in canine mammary gland tumor
Soyeon Cho1,2, Na-Yon Kim1, Yeseul Yang1,2
1Laboratory of Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Importance:
Chemokines and their receptors play integral roles in carcinogenesis. CXC motif chemokine receptor 3 (CXCR3) in T cells mediates anti-tumor effects, whereas CXCR3 in malignant cells promotes proliferation and metastasis. Although the role of CXCR3 has been well-documented in human cancers, including breast cancer, its function in canine tumors remains largely unexplored.
Objective:
This study aimed to investigate the effects of CXCR3 and its ligand interaction in canine mammary gland tumor (cMGT) cells.
Methods:
CXCR3 expression in two cMGT cell lines, CIPp and CIPm, was evaluated using real-time quantitative polymerase chain reaction, western blotting, and flow cytometry. CXC motif chemokine ligand 10 (CXCL10)-induced changes in CXCR3 protein expression in cMGT cells were assessed using membrane fractionation assays. Cell proliferation and migration in response to CXCL10 treatment were analyzed using Cell Counting Kit-8 and wound-healing assays, respectively. Additionally, the downstream molecular mechanisms of the CXCL10/CXCR3 axis were examined.
Results:
CXCR3 expression was significantly higher in CIPm than in CIPp cells. In both the cMGT cell lines, CXCL10 treatment reduced CXCR3 expression on the cell membrane in a dose- and time-dependent manner. The CXCR10/CXCR3 axis promoted cell proliferation and migration in cMGT cells. CXCL10/CXCR3 interaction upregulated the phosphorylation of AKT1 and ERK.
Conclusions And Relevance:
This study demonstrates that the CXCL10/CXCR3 axis may contribute to the pathogenesis of cMGTs by promoting tumor cell proliferation and migration. CXCR3 signaling represents a potential therapeutic target for cMGTs.
