Evaluation of the influence of the C-X-C motif chemokine ligand 12 / C-X-C chemokine receptor 4 axis on canine mammary gland tumor cell migration

C-X-C motif chemokine ligand 12 (CXCL12) is one of the chemokines that binds to C-X-C chemokine receptor 4 (CXCR4) on tumor cell membranes and induces chemotaxis and/or migration. Mammary gland tumors (MGT) are the most common neoplasms in intact female dogs, with local invasion and distant metastasis regarded as problems. However, the influence of the CXCL12/CXCR4 axis on canine MGT cell migration has not been elucidated. This study aimed to evaluate the expression of CXCL12 and CXCR4 in canine MGT cells and tissues and investigate the influence of CXCL12 protein on the migratory ability of MGT cells. CXCL12 expression was evaluated in 10 canine malignant MGT tissues. CXCL12 expression in tumor cells was identified in all examined tissues; however, the staining pattern and intensity differed between the tumors. Immunocytochemistry revealed three canine MGT cell lines as CXCR4-positive. Migratory ability was evaluated using a wound healing assay, and the migration of CXCR4-positive MGT cells was significantly activated by the addition of CXCL12 protein. This influence was canceled by pre-treatment with a CXCR4 antagonist. The results of our study suggest that the CXCL12/CXCR4 axis may be associated with the migration of canine MGT.