Protumor effect of CXCL10/CXCR3 axis in canine mammary gland tumor.

Abstract

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.